References
- Xu H, Wang Y, Lin S, et al. PTMD: a database of human disease-associated post-translational modifications. Genomics, Proteomics & Bioinformatics. 2018;16(4):244–251.
- Deribe YL, Pawson T, Dikic I. Post-translational modifications in signal integration. Nat Struct Mol Biol. 2010;17(6):666–672.
- Wang YC, Peterson SE, Loring JF. Protein post-translational modifications and regulation of pluripotency in human stem cells. Cell Res. 2014;24(2):143–160.
- Hunter T. Why nature chose phosphate to modify proteins. Philos Trans R Soc Lond B Biol Sci. 2012;367(1602):2513–2516.
- Karthikeyan S, Zhou Q, Osterman AL, et al. Ligand binding-induced conformational changes in riboflavin kinase: structural basis for the ordered mechanism. Biochemistry. 2003;42(43):12532–12538.
- Topolcan O, Holubec L Jr. The role of thymidine kinase in cancer diseases. Expert Opin Med Diagn. 2008;2(2):129–141.
- Heath CM, Stahl PD, Barbieri MA. Lipid kinases play crucial and multiple roles in membrane trafficking and signaling. Histol Histopathol. 2003;18(3):989–998.
- Fabbro D, Cowan-Jacob SW, Moebitz H. Ten things you should know about protein kinases: IUPHAR review 14. Br J Pharmacol. 2015;172:2675–2700.
- Li X, Wilmanns M, Thornton J, et al. Elucidating human phosphatase-substrate networks. Sci Signal. 2013;6(275):rs10.
- Cohen P. The structure and regulation of protein phosphatases. Annu Rev Biochem. 1989;58(1):453–508.
- Roy J, Cyert MS. Cracking the phosphatase code: docking interactions determine substrate specificity. Sci Signal. 2009;2(100):re9.
- Sacco F, Perfetto L, Castagnoli L, et al. The human phosphatase interactome: an intricate family portrait. FEBS Lett. 2012;586(17):2732–2739.
- Shi Y. Serine/threonine phosphatases: mechanism through structure. Cell. 2009;139(3):468–484.
- Hardman G, Perkins S, Brownridge PJ, et al. Strong anion exchange-mediated phosphoproteomics reveals extensive human non-canonical phosphorylation. Embo J. 2019;38(21):e100847.
- Nakatogawa H. Mechanisms governing autophagosome biogenesis. Nat Rev Mol Cell Biol. 2020;21:439–458.
- Jing K, Lim K. Why is autophagy important in human diseases? Exp Mol Med. 2012;44(2):69–72.
- Levine B, Kroemer G. Biological functions of autophagy genes: a disease perspective. Cell. 2019;176:11–42.
- Mizushima N, Levine B, Cuervo AM, et al. Autophagy fights disease through cellular self-digestion. Nature. 2008;451(7182):1069–1075.
- Van Beek N, Klionsky DJ, Reggiori F. Genetic aberrations in macroautophagy genes leading to diseases. Biochim Biophys Acta. 2018;1865(5):803–816.
- Kirkin V, Rogov VV. A diversity of selective autophagy receptors determines the specificity of the autophagy pathway. Mol Cell. 2019;76(2):268–285.
- Gonzalez A, Hall MN. Nutrient sensing and TOR signaling in yeast and mammals. Embo J. 2017;36(4):397–408.
- Reggiori F, Klionsky DJ. Autophagy in the eukaryotic cell. Eukaryot Cell. 2002;1(1):11–21.
- Klionsky DJ, Cregg JM, Dunn WA Jr., et al. A unified nomenclature for yeast autophagy-related genes. Dev Cell. 2003;5(4):539–545.
- Kim J, Huang W-P, Stromhaug PE, et al. Convergence of multiple autophagy and cytoplasm to vacuole targeting components to a perivacuolar membrane compartment prior to de novo vesicle formation. J Biol Chem. 2002;277(1):763–773.
- Suzuki K, Akioka M, Kondo-Kakuta C, et al. Fine mapping of autophagy-related proteins during autophagosome formation in Saccharomyces cerevisiae. J Cell Sci. 2013;126(11):2534–2544.
- Suzuki K, Kirisako T, Kamada Y, et al. The pre-autophagosomal structure organized by concerted functions of APG genes is essential for autophagosome formation. Embo J. 2001;20(21):5971–5981.
- Graef M, Friedman JR, Graham C, et al. ER exit sites are physical and functional core autophagosome biogenesis components. Mol Biol Cell. 2013;24(18):2918–2931.
- Axe EL, Walker SA, Manifava M, et al. Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum. J Cell Biol. 2008;182(4):685–701.
- Yla-Anttila P, Vihinen H, Jokitalo E, et al. 3D tomography reveals connections between the phagophore and endoplasmic reticulum. Autophagy. 2009;5(8):1180–1185.
- Hayashi-Nishino M, Fujita N, Noda T, et al. A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formation. Nat Cell Biol. 2009;11(12):1433–1437.
- Hollenstein DM, Gomez-Sanchez R, Ciftci A, et al. Vac8 spatially confines autophagosome formation at the vacuole in S. cerevisiae. J Cell Sci. 2019;132(22):jcs235002.
- Suzuki K, Kubota Y, Sekito T, et al. Hierarchy of Atg proteins in pre-autophagosomal structure organization. Genes Cells. 2007;12(2):209–218.
- Matsuura A, Tsukada M, Wada Y, et al. Apg1p, a novel protein kinase required for the autophagic process in Saccharomyces cerevisiae. Gene. 1997;192(2):245–250.
- Torggler R, Papinski D, Brach T, et al. Two Independent pathways within selective autophagy converge to activate Atg1 kinase at the vacuole. Mol Cell. 2016;64(2):221–235.
- Kawamata T, Kamada Y, Kabeya Y, et al. Organization of the pre-autophagosomal structure responsible for autophagosome formation. Mol Biol Cell. 2008;19(5):2039–2050.
- Kamada Y, Funakoshi T, Shintani T, et al. Tor-mediated induction of autophagy via an Apg1 protein kinase complex. J Cell Biol. 2000;150(6):1507–1513.
- Yamamoto H, Fujioka Y, Suzuki SW, et al. The Intrinsically disordered protein Atg13 mediates supramolecular assembly of autophagy initiation complexes. Dev Cell. 2016;38(1):86–99.
- Kabeya Y, Kamada Y, Baba M, et al. Atg17 functions in cooperation with Atg1 and Atg13 in yeast autophagy. Mol Biol Cell. 2005;16(5):2544–2553.
- Kijanska M, Dohnal I, Reiter W, et al. Activation of Atg1 kinase in autophagy by regulated phosphorylation. Autophagy. 2010;6(8):1168–1178.
- Yeh YY, Wrasman K, Herman PK. Autophosphorylation within the Atg1 activation loop is required for both kinase activity and the induction of autophagy in saccharomyces cerevisiae. Genetics. 2010;185(3):871–882.
- Fujioka Y, Alam JM, Noshiro D, et al. Phase separation organizes the site of autophagosome formation. Nature. 2020;578(7794):301–305.
- Young AR, Chan E, Hu XW, et al. Starvation and ULK1-dependent cycling of mammalian Atg9 between the TGN and endosomes. J Cell Sci. 2006;119(18):3888–3900.
- Hosokawa N, Hara T, Kaizuka T, et al. Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy [research support, non-U.S. Gov’t]. Mol Biol Cell. 2009;20(7):1981–1991.
- Hara T, Takamura A, Kishi C, et al. FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells. J Cell Biol. 2008;181(3):497–510.
- Ganley IG, Lam Du H, Wang J, et al. ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy. J Biol Chem. 2009;284(18):12297–12305.
- Jung CH, Jun CB, Ro SH, et al. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell. 2009;20(7):1992–2003.
- Ravenhill BJ, Boyle KB, Von Muhlinen N, et al. The cargo receptor NDP52 initiates selective autophagy by recruiting the ULK complex to cytosol-invading bacteria. Mol Cell. 2019;74(2):320–329.
- Lazarus MB, Novotny CJ, Shokat KM. Structure of the human autophagy initiating kinase ULK1 in complex with potent inhibitors. ACS Chem Biol. 2015;10(1):257–261.
- Dorsey FC, Rose KL, Coenen S, et al. Mapping the phosphorylation sites of Ulk1. J Proteome Res. 2009;8(11):5253–5263.
- Liu CC, Lin YC, Chen YH, et al. Cul3-KLHL20 ubiquitin ligase governs the turnover of ULK1 and VPS34 complexes to control autophagy termination. Mol Cell. 2016;61(1):84–97.
- Budovskaya YV, Stephan JS, Deminoff SJ, et al. An evolutionary proteomics approach identifies substrates of the cAMP-dependent protein kinase. Proc Natl Acad Sci U S A. 2005;102(39):13933–13938.
- Yeh YY, Shah KH, Chou CC, et al. The identification and analysis of phosphorylation sites on the Atg1 protein kinase. Autophagy. 2011;7(7):716–726.
- Hu Z, Raucci S, Jaquenoud M, et al. Multilayered control of protein turnover by TORC1 and Atg1. Cell Rep. 2019;28(13):3486–3496.
- Shang L, Chen S, Du F, et al. Nutrient starvation elicits an acute autophagic response mediated by Ulk1 dephosphorylation and its subsequent dissociation from AMPK. Proc Natl Acad Sci U S A. 2011;108(12):4788–4793.
- Wong PM, Feng Y, Wang J, et al. Regulation of autophagy by coordinated action of mTORC1 and protein phosphatase 2A. Nat Commun. 2015;6(1):8048.
- Torii S, Yoshida T, Arakawa S, et al. Identification of PPM1D as an essential Ulk1 phosphatase for genotoxic stress-induced autophagy. EMBO Rep. 2016;17(11):1552–1564.
- Torii S, Yamaguchi H, Nakanishi A, et al. Identification of a phosphorylation site on Ulk1 required for genotoxic stress-induced alternative autophagy. Nat Commun. 2020;11(1):1754.
- Kim J, Kundu M, Viollet B, et al. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1 [research support, N.I.H., Extramural]. Nat Cell Biol. 2011;13(2):132–141.
- Egan DF, Shackelford DB, Mihaylova MM, et al. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science. 2011;331(6016):456–461.
- Mack HI, Zheng B, Asara J, et al. AMPK-dependent phosphorylation of ULK1 regulates ATG9 localization. Autophagy. 2012;8(8):1197–1214.
- Odle RI, Walker SA, Oxley D, et al. An mTORC1-to-CDK1 switch maintains autophagy suppression during mitosis. Mol Cell. 2020;77(2):228–240.
- Li Z, Tian X, Ji X, et al. ULK1-ATG13 and their mitotic phospho-regulation by CDK1 connect autophagy to cell cycle. PLoS Biol. 2020;18(6):e3000288.
- Lu H, Xiao J, Ke C, et al. TOPK inhibits autophagy by phosphorylating ULK1 and promotes glioma resistance to TMZ. Cell Death Dis. 2019;10(8):583.
- Bach M, Larance M, James DE, et al. The serine/threonine kinase ULK1 is a target of multiple phosphorylation events. Biochem J. 2011;440(2):283–291.
- Kamada Y, Yoshino K, Kondo C, et al. Tor directly controls the Atg1 kinase complex to regulate autophagy. Mol Cell Biol. 2010;30(4):1049–1058.
- Fujioka Y, Suzuki SW, Yamamoto H, et al. Structural basis of starvation-induced assembly of the autophagy initiation complex. Nat Struct Mol Biol. 2014;21(6):513–521.
- Rao Y, Perna MG, Hofmann B, et al. The Atg1-kinase complex tethers Atg9-vesicles to initiate autophagy. Nat Commun. 2016;7(1):10338.
- Stephan JS, Yeh YY, Ramachandran V, et al. The Tor and PKA signaling pathways independently target the Atg1/Atg13 protein kinase complex to control autophagy. Proc Natl Acad Sci U S A. 2009;106(40):17049–17054.
- Mercer CA, Kaliappan A, Dennis PB. A novel, human Atg13 binding protein, Atg101, interacts with ULK1 and is essential for macroautophagy. Autophagy. 2009;5(5):649–662.
- Puente C, Hendrickson RC, Jiang X. Nutrient-regulated phosphorylation of ATG13 inhibits starvation-induced autophagy. J Biol Chem. 2016;291(11):6026–6035.
- Joo JH, Dorsey FC, Joshi A, et al. Hsp90-Cdc37 chaperone complex regulates Ulk1- and Atg13-mediated mitophagy. Mol Cell. 2011;43(4):572–585.
- Egan DF, Chun MG, Vamos M, et al. Small molecule inhibition of the autophagy kinase ULK1 and identification of ULK1 substrates. Mol Cell. 2015;59(2):285–297.
- Mao K, Chew LH, Inoue-Aono Y, et al. Atg29 phosphorylation regulates coordination of the Atg17-Atg31-Atg29 complex with the Atg11 scaffold during autophagy initiation. Proc Natl Acad Sci U S A. 2013;110(31):E2875–84.
- Yao W, Li Y, Wu L, et al. Atg11 is required for initiation of glucose starvation-induced autophagy. Autophagy. 2020;16(12):2206–2218.
- Feng W, Wu T, Dan X, et al. Phosphorylation of Atg31 is required for autophagy. Protein Cell. 2015;6(4):288–296.
- Chen S, Wang C, Yeo S, et al. Distinct roles of autophagy-dependent and -independent functions of FIP200 revealed by generation and analysis of a mutant knock-in mouse model. Genes Dev. 2016;30(7):856–869.
- Hara T, Mizushima N. Role of ULK-FIP200 complex in mammalian autophagy: FIP200, a counterpart of yeast Atg17? Autophagy. 2009;5(1):85–87.
- Li F, Chung T, Vierstra RD. AUTOPHAGY-RELATED11 plays a critical role in general autophagy- and senescence-induced mitophagy in arabidopsis. Plant Cell. 2014;26(2):788–807.
- Steffan JS. Does Huntingtin play a role in selective macroautophagy? Cell Cycle. 2010;9(17):3401–3413.
- Nishimura T, Tamura N, Kono N, et al. Autophagosome formation is initiated at phosphatidylinositol synthase-enriched ER subdomains. Embo J. 2017;36(12):1719–1735.
- Turco E, Witt M, Abert C, et al. FIP200 claw domain binding to p62 promotes autophagosome formation at ubiquitin condensates. Mol Cell. 2019;74(2):330–346.
- Vargas JNS, Wang C, Bunker E, et al. Spatiotemporal control of ULK1 activation by NDP52 and TBK1 during selective autophagy. Mol Cell. 2019;74(2):347–362.
- Smith MD, Harley ME, Kemp AJ, et al. CCPG1 Is a non-canonical autophagy cargo receptor essential for ER-phagy and pancreatic ER proteostasis. Dev Cell. 2018;44(2):217–232.
- Suzuki H, Kaizuka T, Mizushima N, et al. Structure of the Atg101-Atg13 complex reveals essential roles of Atg101 in autophagy initiation. Nat Struct Mol Biol. 2015;22(7):572–580.
- Janssens V, Goris J. Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling. Biochem J. 2001;353(3):417–439.
- Ronne H, Carlberg M, Hu GZ, et al. Protein phosphatase 2A in Saccharomyces cerevisiae: effects on cell growth and bud morphogenesisMol Cell Biol. 1991;11(10):4876–4884.
- Lin FC, Arndt KT. The role of Saccharomyces cerevisiae type 2A phosphatase in the actin cytoskeleton and in entry into mitosisEmbo J. 1995;14(12):2745–2759.
- Wei H, Ashby DG, Moreno CS, et al. Carboxymethylation of the PP2A catalytic subunit in Saccharomyces cerevisiae is required for efficient interaction with the B-type subunits Cdc55p and Rts1p. J Biol Chem. 2001;276(2):1570–1577.
- Zabrocki P, Van Hoof C, Goris J, et al. Protein phosphatase 2A on track for nutrient-induced signalling in yeast. Mol Microbiol. 2002;43(4):835–842.
- Di Como CJ, Arndt KT. Nutrients, via the Tor proteins, stimulate the association of Tap42 with type 2A phosphatases. Genes Dev. 1996;10(15):1904–1916.
- Jiang Y, Broach JR. Tor proteins and protein phosphatase 2A reciprocally regulate Tap42 in controlling cell growth in yeast. Embo J. 1999;18(10):2782–2792.
- Yeasmin AM, Waliullah TM, Kondo A, et al. Orchestrated action of PP2A antagonizes Atg13 phosphorylation and promotes autophagy after the inactivation of TORC1. PLoS One. 2016;11(12):e0166636.
- Yorimitsu T, He C, Wang K, et al. Tap42-associated protein phosphatase type 2A negatively regulates induction of autophagy. Autophagy. 2009;5(5):616–624.
- Arino J, Velazquez D, Casamayor A. Ser/Thr protein phosphatases in fungi: structure, regulation and function. Microb Cell. 2019;6(5):217–256.
- Schuhmacher D, Sontag JM, Sontag E. Protein phosphatase 2A: more than a passenger in the regulation of epithelial cell-cell junctions. Front Cell Dev Biol. 2019;7:30.
- Taylor GS, Liu Y, Baskerville C, et al. The activity of Cdc14p, an oligomeric dual specificity protein phosphatase from Saccharomyces cerevisiae, is required for cell cycle progression. J Biol Chem. 1997;272(38):24054–24063.
- Kondo A, Mostofa MG, Miyake K, et al. Cdc14 phosphatase promotes TORC1-regulated autophagy in yeast. J Mol Biol. 2018;430(11):1671–1684.
- Gray CH, Good V, Tonks N, et al. The structure of the cell cycle protein Cdc14 reveals a proline-directed protein phosphatase. Embo J. 2003;22(14):3524–3535.
- Manzano-Lopez J, Monje-Casas F. The multiple roles of the Cdc14 phosphatase in cell cycle control. Int J Mol Sci. 2020;21(3):709.
- Li L, Ernsting BR, Wishart MJ, et al. A family of putative tumor suppressors is structurally and functionally conserved in humans and yeast. J Biol Chem. 1997;272(47):29403–29406.
- Ruan H, Yan Z, Sun H, et al. The YCR079w gene confers a rapamycin-resistant function and encodes the sixth type 2C protein phosphatase in Saccharomyces cerevisiae. FEMS Yeast Res. 2007;7(2):209–215.
- Jiang L, Whiteway M, Ramos C, et al. The YHR076w gene encodes a type 2C protein phosphatase and represents the seventh PP2C gene in budding yeast. FEBS Lett. 2002;527(1–3):323–325.
- Cheng A, Ross KE, Kaldis P, et al. Dephosphorylation of cyclin-dependent kinases by type 2C protein phosphatases. Genes Dev. 1999;13(22):2946–2957.
- Arino J, Casamayor A, Gonzalez A. Type 2C protein phosphatases in fungi. Eukaryot Cell. 2011;10(1):21–33.
- Young C, Mapes J, Hanneman J, et al. Role of Ptc2 type 2C Ser/Thr phosphatase in yeast high-osmolarity glycerol pathway inactivation. Eukaryot Cell. 2002;1(6):1032–1040.
- Warmka J, Hanneman J, Lee J, et al. Ptc1, a type 2C Ser/Thr phosphatase, inactivates the HOG pathway by dephosphorylating the mitogen-activated protein kinase Hog1. Mol Cell Biol. 2001;21(1):51–60.
- Maeda T, Wurgler-Murphy SM, Saito H. A two-component system that regulates an osmosensing MAP kinase cascade in yeast. Nature. 1994;369(6477):242–245.
- Welihinda AA, Tirasophon W, Green SR, et al. Protein serine/threonine phosphatase Ptc2p negatively regulates the unfolded-protein response by dephosphorylating Ire1p kinase. Mol Cell Biol. 1998;18(4):1967–1977.
- Leroy C, Lee SE, Vaze MB, et al. PP2C phosphatases Ptc2 and Ptc3 are required for DNA checkpoint inactivation after a double-strand break. Mol Cell. 2003;11(3):827–835.
- Memisoglu G, Eapen VV, Yang Y, et al. PP2C phosphatases promote autophagy by dephosphorylation of the Atg1 complex. Proc Natl Acad Sci U S A. 2019;116(5):1613–1620.
- Lammers T, Lavi S. Role of type 2C protein phosphatases in growth regulation and in cellular stress signaling. Crit Rev Biochem Mol Biol. 2007;42(6):437–461.
- Papinski D, Schuschnig M, Reiter W, et al. Early steps in autophagy depend on direct phosphorylation of Atg9 by the Atg1 kinase. Mol Cell. 2014;53(3):471–483.
- Yamamoto H, Kakuta S, Watanabe TM, et al. Atg9 vesicles are an important membrane source during early steps of autophagosome formation. J Cell Biol. 2012;198(2):219–233.
- Mari M, Griffith J, Rieter E, et al. An Atg9-containing compartment that functions in the early steps of autophagosome biogenesis. J Cell Biol. 2010;190(6):1005–1022.
- Reggiori F, Tucker KA, Stromhaug PE, et al. The Atg1-Atg13 complex regulates Atg9 and Atg23 retrieval transport from the pre-autophagosomal structure. Dev Cell. 2004;6(1):79–90.
- Feng Y, Backues SK, Baba M, et al. Phosphorylation of Atg9 regulates movement to the phagophore assembly site and the rate of autophagosome formation. Autophagy. 2016;12(4):648–658.
- Zhou C, Ma K, Gao R, et al. Regulation of mATG9 trafficking by Src- and ULK1-mediated phosphorylation in basal and starvation-induced autophagy. Cell Res. 2017;27(2):184–201.
- Weerasekara VK, Panek DJ, Broadbent DG, et al. Metabolic-stress-induced rearrangement of the 14-3-3zeta interactome promotes autophagy via a ULK1- and AMPK-regulated 14-3-3zeta interaction with phosphorylated Atg9. Mol Cell Biol. 2014;34(24):4379–4388.
- Matsunaga K, Saitoh T, Tabata K, et al. Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages. Nat Cell Biol. 2009;11(4):385–396.
- Itakura E, Mizushima N. Characterization of autophagosome formation site by a hierarchical analysis of mammalian Atg proteins. Autophagy. 2010;6(6):764–776.
- Vicinanza M, Korolchuk VI, Ashkenazi A, et al. PI(5)P regulates autophagosome biogenesis. Mol Cell. 2015;57(2):219–234.
- Kamber RA, Shoemaker CJ, Denic V. Receptor-bound targets of selective autophagy use a scaffold protein to activate the Atg1 kinase. Mol Cell. 2015;59(3):372–381.
- Park JM, Jung CH, Seo M, et al. The ULK1 complex mediates MTORC1 signaling to the autophagy initiation machinery via binding and phosphorylating ATG14. Autophagy. 2016;12(3):547–564.
- Wold MS, Lim J, Lachance V, et al. ULK1-mediated phosphorylation of ATG14 promotes autophagy and is impaired in Huntington’s disease models. Mol Neurodegener. 2016;11(1):76.
- Yuan HX, Russell RC, Guan KL. Regulation of PIK3C3/VPS34 complexes by MTOR in nutrient stress-induced autophagy. Autophagy. 2013;9(12):1983–1995.
- Di Bartolomeo S, Corazzari M, Nazio F, et al. The dynamic interaction of AMBRA1 with the dynein motor complex regulates mammalian autophagy [research support, non-U.S. Gov’t]. J Cell Biol. 2010;191(1):155–168.
- Furuya T, Kim M, Lipinski M, et al. Negative regulation of Vps34 by Cdk mediated phosphorylation. Mol Cell. 2010;38(4):500–511.
- Eisenberg-Lerner A, Kimchi A. PKD is a kinase of Vps34 that mediates ROS-induced autophagy downstream of DAPk. Cell Death Differ. 2012;19(5):788–797.
- Fujiwara N, Usui T, Ohama T, et al. Regulation of Beclin 1 protein phosphorylation and autophagy by protein phosphatase 2A (PP2A) and death-associated protein kinase 3 (DAPK3). J Biol Chem. 2016;291(20):10858–10866.
- Menon MB, Dhamija S. Beclin 1 phosphorylation - at the center of autophagy regulation. Front Cell Dev Biol. 2018;6:137.
- Hill SM, Wrobel L, Rubinsztein DC. Post-translational modifications of Beclin 1 provide multiple strategies for autophagy regulation. Cell Death Differ. 2019;26(4):617–629.
- Lu J, He L, Behrends C, et al. NRBF2 regulates autophagy and prevents liver injury by modulating Atg14L-linked phosphatidylinositol-3 kinase III activity. Nat Commun. 2014;5(1):3920.
- Zhong Y, Morris DH, Jin L, et al. Nrbf2 protein suppresses autophagy by modulating Atg14L protein-containing Beclin 1-Vps34 complex architecture and reducing intracellular phosphatidylinositol-3 phosphate levels. J Biol Chem. 2014;289(38):26021–26037.
- Araki Y, Ku WC, Akioka M, et al. Atg38 is required for autophagy-specific phosphatidylinositol 3-kinase complex integrity. J Cell Biol. 2013;203(2):299–313.
- Cao Y, Wang Y, Abi Saab WF, et al. NRBF2 regulates macroautophagy as a component of Vps34 complex I. Biochem J. 2014;461(2):315–322.
- Ma X, Zhang S, He L, et al. MTORC1-mediated NRBF2 phosphorylation functions as a switch for the class III PtdIns3K and autophagy. Autophagy. 2017;13(3):592–607.
- Proikas-Cezanne T, Waddell S, Gaugel A, et al. WIPI-1a (WIPI49), a member of the novel 7-bladed WIPI protein family, is aberrantly expressed in human cancer and is linked to starvation-induced autophagy. Oncogene. 2004;23(58):9314–9325.
- Polson HE, De Lartigue J, Rigden DJ, et al. Mammalian Atg18 (WIPI2) localizes to omegasome-anchored phagophores and positively regulates LC3 lipidation. Autophagy. 2010;6(4):506–522.
- Krick R, Tolstrup J, Appelles A, et al. The relevance of the phosphatidylinositolphosphat-binding motif FRRGT of Atg18 and Atg21 for the Cvt pathway and autophagy. FEBS Lett. 2006;580(19):4632–4638.
- Wan W, You Z, Zhou L, et al. mTORC1-regulated and HUWE1-mediated WIPI2 degradation controls autophagy flux. Mol Cell. 2018;72(2):303–315.
- Obara K, Sekito T, Niimi K, et al. The Atg18-Atg2 complex is recruited to autophagic membranes via phosphatidylinositol 3-phosphate and exerts an essential function. J Biol Chem. 2008;283(35):23972–23980.
- Papinski D, Kraft C. Atg1 kinase organizes autophagosome formation by phosphorylating Atg9. Autophagy. 2014;10(7):1338–1340.
- Mizushima N. The ATG conjugation systems in autophagy. Curr Opin Cell Biol. 2020;63:1–10.
- Dooley HC, Razi M, Polson HE, et al. WIPI2 links LC3 conjugation with PI3P, autophagosome formation, and pathogen clearance by recruiting Atg12-5-16L1. Mol Cell. 2014;55(2):238–252.
- Diamanti MA, Gupta J, Bennecke M, et al. IKKalpha controls ATG16L1 degradation to prevent ER stress during inflammation. J Exp Med. 2017;214(2):423–437.
- Alsaadi RM, Losier TT, Tian W, et al. ULK1-mediated phosphorylation of ATG16L1 promotes xenophagy, but destabilizes the ATG16L1 Crohn’s mutant. EMBO Rep. 2019;20(7):e46885.
- Zhao X, Nedvetsky P, Stanchi F, et al. Endothelial PKA activity regulates angiogenesis by limiting autophagy through phosphorylation of ATG16L1. Elife. 2019;8:e46380.
- Song H, Pu J, Wang L, et al. ATG16L1 phosphorylation is oppositely regulated by CSNK2/casein kinase 2 and PPP1/protein phosphatase 1 which determines the fate of cardiomyocytes during hypoxia/reoxygenation. Autophagy. 2015;11(8):1308–1325.
- Feng X, Zhang H, Meng L, et al. Hypoxia-induced acetylation of PAK1 enhances autophagy and promotes brain tumorigenesis via phosphorylating ATG5. Autophagy. 2021;17(3):723–742.
- Keil E, Hocker R, Schuster M, et al. Phosphorylation of Atg5 by the Gadd45beta-MEKK4-p38 pathway inhibits autophagy. Cell Death Differ. 2013;20(2):321–332.
- Herhaus L, Bhaskara RM, Lystad AH, et al. TBK1-mediated phosphorylation of LC3C and GABARAP-L2 controls autophagosome shedding by ATG4 protease. EMBO Rep. 2020;21(1):e48317.
- Cherra SJ 3rd, Kulich SM, Uechi G, et al. Regulation of the autophagy protein LC3 by phosphorylation. J Cell Biol. 2010;190(4):533–539.
- Shrestha BK, Skytte Rasmussen M, Abudu YP, et al. NIMA-related kinase 9-mediated phosphorylation of the microtubule-associated LC3B protein at Thr-50 suppresses selective autophagy of p62/sequestosome 1. J Biol Chem. 2020;295(5):1240–1260.
- Wilkinson DS, Jariwala JS, Anderson E, et al. Phosphorylation of LC3 by the Hippo kinases STK3/STK4 is essential for autophagy. Mol Cell. 2015;57(1):55–68.
- Nakatogawa H, Ishii J, Asai E, et al. Atg4 recycles inappropriately lipidated Atg8 to promote autophagosome biogenesis [Research Support, Non-U.S. Gov’t]. Autophagy. 2012;8(2):177–186.
- Abreu S, Kriegenburg F, Gómez‐Sánchez R, et al. Conserved Atg8 recognition sites mediate Atg4 association with autophagosomal membranes and Atg8 deconjugation. EMBO reports. 2017;18(5):765–780.
- Nair U, Yen WL, Mari M, et al. A role for Atg8-PE deconjugation in autophagosome biogenesis. Autophagy. 2012;8(5):780–793.
- Sanchez-Wandelmer J, Kriegenburg F, Rohringer S, et al. Atg4 proteolytic activity can be inhibited by Atg1 phosphorylation. Nat Commun. 2017;8(1):295.
- Pengo N, Agrotis A, Prak K, et al. A reversible phospho-switch mediated by ULK1 regulates the activity of autophagy protease ATG4B. Nat Commun. 2017;8(1):294.
- Ni Z, He J, Wu Y, et al. AKT-mediated phosphorylation of ATG4B impairs mitochondrial activity and enhances the Warburg effect in hepatocellular carcinoma cells. Autophagy. 2018;14(4):685–701.
- Pengo N, Prak K, Costa JR, et al. Identification of kinases and phosphatases that regulate ATG4B activity by siRNA and small molecule screening in cells. Front Cell Dev Biol. 2018;6:148.
- Huang T, Kim CK, Alvarez AA, et al. MST4 phosphorylation of ATG4B regulates autophagic activity, tumorigenicity, and radioresistance in glioblastoma. Cancer Cell. 2017;32(6):840–855.
- Yang Z, Wilkie-Grantham RP, Yanagi T, et al. ATG4B (Autophagin-1) phosphorylation modulates autophagy. J Biol Chem. 2015;290(44):26549–26561.
- Kerk D, Moorhead GB. A phylogenetic survey of myotubularin genes of eukaryotes: distribution, protein structure, evolution, and gene expression. BMC Evol Biol. 2010;10(1):196.
- Hughes WE, Cooke FT, Parker PJ. Sac phosphatase domain proteins. Biochem J. 2000;350(2):337–352.
- Nandurkar HH, Huysmans R. The myotubularin family: novel phosphoinositide regulators. IUBMB Life. 2002;53(1):37–43.
- Schaletzky J, Dove SK, Short B, et al. Phosphatidylinositol-5-phosphate activation and conserved substrate specificity of the myotubularin phosphatidylinositol 3-phosphatases. Curr Biol. 2003;13(6):504–509.
- Parrish WR, Stefan CJ, Emr SD. Essential role for the myotubularin-related phosphatase Ymr1p and the synaptojanin-like phosphatases Sjl2p and Sjl3p in regulation of phosphatidylinositol 3-phosphate in yeast. Mol Biol Cell. 2004;15(8):3567–3579.
- Laporte J, Bedez F, Bolino A, et al. Myotubularins, a large disease-associated family of cooperating catalytically active and inactive phosphoinositides phosphatases. Hum Mol Genet. 2003;12(2):R285–92.
- Cebollero E, Van Der Vaart A, Zhao M, et al. Phosphatidylinositol-3-phosphate clearance plays a key role in autophagosome completion. Curr Biol. 2012;22(17):1545–1553.
- Wu Y, Cheng S, Zhao H, et al. PI3P phosphatase activity is required for autophagosome maturation and autolysosome formation. EMBO Rep. 2014;15(9):973–981.
- Allen EA, Amato C, Fortier TM, et al. A conserved myotubularin-related phosphatase regulates autophagy by maintaining autophagic flux. J Cell Biol. 2020;219(11):e201909073.
- Itoh T, Takenawa T. Phosphoinositide-binding domains: functional units for temporal and spatial regulation of intracellular signalling. Cell Signal. 2002;14(9):733–743.
- Taguchi-Atarashi N, Hamasaki M, Matsunaga K, et al. Modulation of local PtdIns3P levels by the PI phosphatase MTMR3 regulates constitutive autophagy. Traffic. 2010;11(4):468–478.
- Vergne I, Roberts E, Elmaoued RA, et al. Control of autophagy initiation by phosphoinositide 3-phosphatase Jumpy. Embo J. 2009;28(15):2244–2258.
- Gibbs EM, Feldman EL, Dowling JJ. The role of MTMR14 in autophagy and in muscle disease. Autophagy. 2010;6(6):819–820.
- Reggiori F, Ungermann C. Autophagosome maturation and fusion. J Mol Biol. 2017;429(4):486–496.
- Zhao YG, Zhang H. Autophagosome maturation: an epic journey from the ER to lysosomes. J Cell Biol. 2019;218(3):757–770.
- Matsui T, Jiang P, Nakano S, et al. Autophagosomal YKT6 is required for fusion with lysosomes independently of syntaxin 17. J Cell Biol. 2018;217(8):2633–2645.
- Bas L, Papinski D, Licheva M, et al. Reconstitution reveals Ykt6 as the autophagosomal SNARE in autophagosome-vacuole fusion. J Cell Biol. 2018;217(10):3656–3669.
- Gao J, Reggiori F, Ungermann C. A novel in vitro assay reveals SNARE topology and the role of Ykt6 in autophagosome fusion with vacuoles. J Cell Biol. 2018;217(10):3670–3682.
- Gao J, Kurre R, Rose J, et al. Function of the SNARE Ykt6 on autophagosomes requires the Dsl1 complex and the Atg1 kinase complex. EMBO Rep. 2020;21(12):e50733.
- Barz S, Kriegenburg F, Henning A, et al. Atg1 kinase regulates autophagosome-vacuole fusion by controlling SNARE bundling. EMBO Rep. 2020;21(12):e51869.
- Wang C, Wang H, Zhang D, et al. Phosphorylation of ULK1 affects autophagosome fusion and links chaperone-mediated autophagy to macroautophagy. Nat Commun. 2018;9(1):3492.
- Kumar S, Gu Y, Abudu YP, et al. Phosphorylation of syntaxin 17 by TBK1 controls autophagy initiation. Dev Cell. 2019;49(1):130–144.
- Kim YM, Jung CH, Seo M, et al. mTORC1 phosphorylates UVRAG to negatively regulate autophagosome and endosome maturation. Mol Cell. 2015;57(2):207–218.
- Cheng X, Ma X, Ding X, et al. Pacer mediates the function of class III PI3K and HOPS complexes in autophagosome maturation by engaging Stx17. Mol Cell. 2017;65(6):1029–1043.
- Audhya A, Emr SD. Stt4 PI 4-kinase localizes to the plasma membrane and functions in the Pkc1-mediated MAP kinase cascade. Dev Cell. 2002;2(5):593–605.
- Strahl T, Hama H, DeWald DB, et al. Yeast phosphatidylinositol 4-kinase, Pik1, has essential roles at the Golgi and in the nucleus. J Cell Biol. 2005;171(6):967–979.
- Han GS, Audhya A, Markley DJ, et al. The Saccharomyces cerevisiae LSB6 gene encodes phosphatidylinositol 4-kinase activity. J Biol Chem. 2002;277(49):47709–47718.
- Wang K, Yang Z, Liu X, et al. Phosphatidylinositol 4-kinases are required for autophagic membrane trafficking. J Biol Chem. 2012;287(45):37964–37972.
- Kurokawa Y, Konishi R, Yoshida A, et al. Essential and distinct roles of phosphatidylinositol 4-kinases, Pik1p and Stt4p, in yeast autophagy. Biochim Biophys Acta Mol Cell Biol Lipids. 2019;1864(9):1214–1225.
- Boura E, Nencka R. Phosphatidylinositol 4-kinases: function, structure, and inhibition. Exp Cell Res. 2015;337(2):136–145.
- Wang H, Sun HQ, Zhu X, et al. GABARAPs regulate PI4P-dependent autophagosome: lysosomefusion. Proc Natl Acad Sci U S A. 2015;112(22):7015–7020.
- Kurokawa Y, Yoshida A, Fujii E, et al. Phosphatidylinositol 4-phosphate on Rab7-positive autophagosomes revealed by the freeze-fracture replica labeling. Traffic. 2019;20(1):82–95.
- Judith D, Jefferies HBJ, Boeing S, et al. ATG9A shapes the forming autophagosome through Arfaptin 2 and phosphatidylinositol 4-kinase IIIbeta. J Cell Biol. 2019;218(5):1634–1652.
- Del Bel LM, Brill JA. Sac1, a lipid phosphatase at the interface of vesicular and nonvesicular transport. Traffic. 2018;19(5):301–318.
- Zhang H, Zhou J, Xiao P, et al. PtdIns4P restriction by hydrolase SAC1 decides specific fusion of autophagosomes with lysosomes. Autophagy. in press 2020;1–11. DOI:https://doi.org/10.1080/15548627.2020.1796321
- Miao G, Zhang Y, Chen D, et al. The ER-localized transmembrane protein TMEM39A/SUSR2 regulates autophagy by controlling the trafficking of the PtdIns(4)P phosphatase SAC1. Mol Cell. 2020;77(3):618–632.
- Xiang H, Zhang J, Lin C, et al. Targeting autophagy-related protein kinases for potential therapeutic purpose. Acta Pharm Sin B. 2020;10(4):569–581.
- Kohn M. Turn and Face the Strange: a New View on Phosphatases. ACS Cent Sci. 2020;6(4):467–477.
- Bertolotti A. The split protein phosphatase system. Biochem J. 2018;475(23):3707–3723.
- Oberstein A, Jeffrey PD, Shi Y. Crystal structure of the Bcl-XL-Beclin 1 peptide complex: beclin 1 is a novel BH3-only protein. J Biol Chem. 2007;282(17):13123–13132.
- Furuya N, Yu J, Byfield M, et al. The evolutionarily conserved domain of beclin 1 is required for Vps34 binding, autophagy, and tumor suppressor function. Autophagy. 2005;1(1):46–52.
- Li X, He L, Che KH, et al. Imperfect interface of Beclin1 coiled-coil domain regulates homodimer and heterodimer formation with Atg14L and UVRAG. Nat Commun. 2012;3(1):662.
- Birgisdottir AB, Mouilleron S, Bhujabal Z, et al. Members of the autophagy class III phosphatidylinositol 3-kinase complex I interact with GABARAP and GABARAPL1 via LIR motifs. Autophagy. 2019;15(8):1333–1355.
- Park JM, Seo M, Jung CH, et al. ULK1 phosphorylates Ser30 of BECN1 in association with ATG14 to stimulate autophagy induction. Autophagy. 2018;14(4):584–597.
- Russell RC, Tian Y, Yuan H, et al. ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase. Nat Cell Biol. 2013;15(7):741–750.
- Kumar A, Shaha C. SESN2 facilitates mitophagy by helping Parkin translocation through ULK1 mediated Beclin1 phosphorylation. Sci Rep. 2018;8(1):615.
- Qian X, Li X, Cai Q, et al. Phosphoglycerate kinase 1 phosphorylates Beclin1 to Induce autophagy. Mol Cell. 2017;65(5):917–931.
- Wei Y, An Z, Zou Z, et al. The stress-responsive kinases MAPKAPK2/MAPKAPK3 activate starvation-induced autophagy through Beclin 1 phosphorylation. Elife. 2015;4:e05289.
- Li X, Wu XQ, Deng R, et al. CaMKII-mediated Beclin 1 phosphorylation regulates autophagy that promotes degradation of Id and neuroblastoma cell differentiation. Nat Commun. 2017;8(1):1159.
- Kim J, Kim YC, Fang C, et al. Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy. Cell. 2013;152(1–2):290–303.
- Maejima Y, Kyoi S, Zhai P, et al. Mst1 inhibits autophagy by promoting the interaction between Beclin1 and Bcl-2. Nat Med. 2013;19(11):1478–1488.
- Shiloh R, Gilad Y, Ber Y, et al. Non-canonical activation of DAPK2 by AMPK constitutes a new pathway linking metabolic stress to autophagy. Nat Commun. 2018;9(1):1759.
- Zalckvar E, Berissi H, Mizrachy L, et al. DAP-kinase-mediated phosphorylation on the BH3 domain of beclin 1 promotes dissociation of beclin 1 from Bcl-XL and induction of autophagy. EMBO Rep. 2009;10(3):285–292.
- Gurkar AU, Chu K, Raj L, et al. Identification of ROCK1 kinase as a critical regulator of Beclin1-mediated autophagy during metabolic stress. Nat Commun. 2013;4(1):2189.
- Wei Y, Zou Z, Becker N, et al. EGFR-mediated Beclin 1 phosphorylation in autophagy suppression, tumor progression, and tumor chemoresistance. Cell. 2013;154(6):1269–1284.
- Cheng Z, Zhu Q, Dee R, et al. Focal adhesion kinase-mediated phosphorylation of beclin1 protein suppresses cardiomyocyte autophagy and initiates hypertrophic growth. J Biol Chem. 2017;292(6):2065–2079.
- Yu C, Gorantla SP, Muller-Rudorf A, et al. Phosphorylation of BECLIN-1 by BCR-ABL suppresses autophagy in chronic myeloid leukemia. Haematologica. 2020;105(5):1285–1293.
- Wang RC, Wei Y, An Z, et al. Akt-mediated regulation of autophagy and tumorigenesis through Beclin 1 phosphorylation. Science. 2012;338(6109):956–959.
- Zhang D, Wang W, Sun X, et al. AMPK regulates autophagy by phosphorylating BECN1 at threonine 388. Autophagy. 2016;12(9):1447–1459.
- Sun T, Li X, Zhang P, et al. Acetylation of Beclin 1 inhibits autophagosome maturation and promotes tumour growth. Nat Commun. 2015;6(1):7215.
- Obara K, Sekito T, Ohsumi Y. Assortment of phosphatidylinositol 3-Kinase complexes—Atg14p directs association of complex I to the pre-autophagosomal structure in Saccharomyces cerevisiae. Mol Biol Cell. 2006;17(4):1527–1539.