727
Views
0
CrossRef citations to date
0
Altmetric
Perspective

The adenoviral protein E4orf4: a probing tool to decipher mechanical stress-induced nuclear envelope remodeling in tumor cells

, , ORCID Icon & ORCID Icon
Pages 2963-2981 | Received 31 Jul 2020, Accepted 07 Oct 2020, Published online: 25 Oct 2020

References

  • Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–674.
  • Pickup MW, Mouw JK, Weaver VM. The extracellular matrix modulates the hallmarks of cancer. EMBO reports. 2014;15(12):1243–1253.
  • Mohammadi H, Sahai E. Mechanisms and impact of altered tumour mechanics. Nat Cell Biol. 2018;20(7):766–774.
  • Butcher DT, Alliston T, Weaver VM. A tense situation: forcing tumour progression. Nat Rev Cancer. 2009;9(2):108–122.
  • Yuan S, Norgard RJ, Stanger BZ. Cellular plasticity in cancer. Cancer Discov. 2019;9(7):837–851.
  • Williams ED, Gao D, Redfern A, et al. Controversies around epithelial-mesenchymal plasticity in cancer metastasis. Nat Rev Cancer. 2019;19(12):716–732.
  • Alibert C, Goud B, Manneville JB. Are cancer cells really softer than normal cells? Biol Cell. 2017;109(5):167–189.
  • Coughlin MF, Bielenberg DR, Lenormand G, et al. Cytoskeletal stiffness, friction, and fluidity of cancer cell lines with different metastatic potential. Clin Exp Metastasis. 2013;30(3):237–250.
  • Kraning-Rush CM, Califano JP, Reinhart-King CA. Cellular traction stresses increase with increasing metastatic potential. PloS One. 2012;7(2):e32572.
  • Panciera T, Citron A, Di Biagio D, et al. Reprogramming normal cells into tumour precursors requires ECM stiffness and oncogene-mediated changes of cell mechanical properties. Nat Mater. 2020;19(7):797.
  • Clayton NS, Ridley AJ. Targeting Rho GTPase signaling networks in cancer. Front Cell Dev Biol. 2020;8:222.
  • Ohashi K, Fujiwara S, Mizuno K. Roles of the cytoskeleton, cell adhesion and rho signalling in mechanosensing and mechanotransduction. J Biochem. 2017;161(3):245–254.
  • Halaoui R, McCaffrey L. Rewiring cell polarity signaling in cancer. Oncogene. 2015;34(8):939–950.
  • Saito Y, Desai RR, Muthuswamy SK. Reinterpreting polarity and cancer: the changing landscape from tumor suppression to tumor promotion. Biochim Biophys Acta Rev Cancer. 2018;1869(2):103–116.
  • Fomicheva M, Tross EM, Macara IG. Polarity proteins in oncogenesis. Curr Opin Cell Biol. 2020;62:26–30.
  • Gandalovičová A, Vomastek T, Rosel, T, et al. Cell polarity signaling in the plasticity of cancer cell invasiveness. Oncotarget. 2016;7(18):25022-49.
  • Wolf K, Te Lindert M, Krause M, et al. Physical limits of cell migration: control by ECM space and nuclear deformation and tuning by proteolysis and traction force. J Cell Biol. 2013;201(7):1069–1084.
  • Davidson PM, Denais C, Bakshi MC, et al. Nuclear deformability constitutes a rate-limiting step during cell migration in 3-D environments. Cell Mol Bioeng. 2014;7(3):293–306.
  • Calero-Cuenca FJ, Janota CS, Gomes ER. Dealing with the nucleus during cell migration. Curr Opin Cell Biol. 2018;50:35–41.
  • Kirby TJ, Lammerding J. Emerging views of the nucleus as a cellular mechanosensor. Nat Cell Biol. 2018;20(4):373–381.
  • Janota CS, Calero-Cuenca FJ, Gomes ER. The role of the cell nucleus in mechanotransduction. Curr Opin Cell Biol. 2020;63:204–211.
  • Bell ES, Lammerding J. Causes and consequences of nuclear envelope alterations in tumour progression. Eur J Cell Biol. 2016;95(11):449–464.
  • Denais C, Lammerding J. Nuclear mechanics in cancer. Adv Exp Med Biol. 2014;773:435–470.
  • Chow KH, Factor RE, Ullman KS. The nuclear envelope environment and its cancer connections. Nat Rev Cancer. 2012;12(3):196–209.
  • Denais CM, Gilbert RM, Isermann P, et al. Nuclear envelope rupture and repair during cancer cell migration. Science. 2016;352(6283):353–358.
  • Raab M, Gentili M, de Belly H, et al. ESCRT III repairs nuclear envelope ruptures during cell migration to limit DNA damage and cell death. Science. 2016;352(6283):359–362.
  • Xia Y, Ivanovska IL, Zhu K, et al. Nuclear rupture at sites of high curvature compromises retention of DNA repair factors. J Cell Biol. 2018;217(11):3796–3808.
  • Vargas JD, Hatch EM, Anderson DJ, et al. Transient nuclear envelope rupturing during interphase in human cancer cells. Nucleus. 2012;3(1):88–100.
  • Pfeifer CR, Vashisth M, Xia Y, et al. Nuclear failure, DNA damage, and cell cycle disruption after migration through small pores: a brief review. Essays Biochem. 2019;63(5):569–577.
  • Shah P, Wolf K, Lammerding J. Bursting the bubble - nuclear envelope rupture as a path to genomic instability? Trends Cell Biol. 2017;27(8):546–555.
  • Maciejowski J, Hatch EM. Nuclear membrane rupture and its consequences. Annu Rev Cell Dev Biol. 2020;36:85-114.
  • De Vos WH, Houben F, Kamps M, et al. Repetitive disruptions of the nuclear envelope invoke temporary loss of cellular compartmentalization in laminopathies. Hum Mol Genet. 2011;20(21):4175–4186.
  • Yang Z, Maciejowski J, de Lange T. Nuclear envelope rupture is enhanced by loss of p53 or Rb. Mol Cancer Res. 2017;15(11):1579–1586.
  • Takaki T, Montagner M, Serres MP, et al. Actomyosin drives cancer cell nuclear dysmorphia and threatens genome stability. Nat Commun. 2017;8(1):16013. .
  • Dick FA, Goodrich DW, Sage J, et al. Non-canonical functions of the RB protein in cancer. Nat Rev Cancer. 2018;18(7):442–451.
  • Eischen CM. Genome Stability Requires p53. Cold Spring Harb Perspect Med. 2016;6(6): a026096
  • Agrawal A, Lele TP. Mechanics of nuclear membranes. J Cell Sci. 2019;132(14): jcs229245.
  • Knockenhauer KE, Schwartz TU. The nuclear pore complex as a flexible and dynamic gate. Cell. 2016;164(6):1162–1171.
  • Osmanagic-Myers S, Dechat T, Foisner R. Lamins at the crossroads of mechanosignaling. Genes Dev. 2015;29(3):225–237.
  • Swift J, Ivanovska IL, Buxboim A, et al. Nuclear lamin-A scales with tissue stiffness and enhances matrix-directed differentiation. Science. 2013;341:1240104.
  • Cho S, Irianto J, Discher DE. Mechanosensing by the nucleus: from pathways to scaling relationships. J Cell Biol. 2017;216:305–315.
  • Alvarado-Kristensson M, Rossello CA. The biology of the nuclear envelope and its implications in cancer biology. Int J Mol Sci. 2019;20(10):2586.
  • Ungricht R, Kutay U. Mechanisms and functions of nuclear envelope remodelling. Nat Rev Mol Cell Biol. 2017;18(4):229–245.
  • De Magistris P, Antonin W. The dynamic nature of the nuclear envelope. Curr Biol. 2018;28(8):R487–R97.
  • Gundersen GG, Worman HJ. Nuclear positioning. Cell. 2013;152(6):1376–1389.
  • Speese SD, Ashley J, Jokhi V, et al. Nuclear envelope budding enables large ribonucleoprotein particle export during synaptic Wnt signaling. Cell. 2012;149(4):832–846.
  • Hellberg T, Passvogel L, Schulz KS, et al. Nuclear egress of herpesviruses: the prototypic vesicular nucleocytoplasmic transport. Adv Virus Res. 2016;94:81–140.
  • Martino F, Perestrelo AR, Vinarsky V, et al. Cellular Mechanotransduction: from Tension to Function. Front Physiol. 2018;9:824.
  • Vogel V, Sheetz M. Local force and geometry sensing regulate cell functions. Nat Rev Mol Cell Biol. 2006;7:265–275.
  • Panciera T, Azzolin L, Cordenonsi M, et al. Mechanobiology of YAP and TAZ in physiology and disease. Nat Rev Mol Cell Biol. 2017;18(12):758–770.
  • Buxboim A, Swift J, Irianto J, et al. Matrix elasticity regulates lamin-A,C phosphorylation and turnover with feedback to actomyosin. Curr Biol. 2014;24:1909–1917.
  • Ihalainen TO, Aires L, Herzog FA, et al. Differential basal-to-apical accessibility of lamin A/C epitopes in the nuclear lamina regulated by changes in cytoskeletal tension. Nat Mater. 2015;14(12):1252–1261.
  • Maniotis AJ, Chen CS, Ingber DE. Demonstration of mechanical connections between integrins, cytoskeletal filaments, and nucleoplasm that stabilize nuclear structure. Proc Natl Acad Sci U S A. 1997;94(3):849–854.
  • Schwager SC, Taufalele PV, Reinhart-King CA. Cell-cell mechanical communication in cancer. Cell Mol Bioeng. 2019;12:1–14.
  • Aureille J, Belaadi N, Guilluy C. Mechanotransduction via the nuclear envelope: a distant reflection of the cell surface. Curr Opin Cell Biol. 2017;44:59–67.
  • Sosa BA, Kutay U, Schwartz TU. Structural insights into LINC complexes. Curr Opin Struct Biol. 2013;23(2):285–291.
  • Chambliss AB, Khatau SB, Erdenberger N, et al. The LINC-anchored actin cap connects the extracellular milieu to the nucleus for ultrafast mechanotransduction. Sci Rep. 2013;3(1):1087.
  • Versaevel M, Braquenier JB, Riaz M, et al. Super-resolution microscopy reveals LINC complex recruitment at nuclear indentation sites. Sci Rep. 2014;4:7362.
  • Luxton GW, Gomes ER, Folker ES, et al. Linear arrays of nuclear envelope proteins harness retrograde actin flow for nuclear movement. Science. 2010;329(5994):956–959.
  • Khatau SB, Hale CM, Stewart-Hutchinson PJ, et al. A perinuclear actin cap regulates nuclear shape. Proc Natl Acad Sci U S A. 2009;106(45):19017–19022.
  • Kim DH, Chambliss AB, Wirtz D. The multi-faceted role of the actin cap in cellular mechanosensation and mechanotransduction. Soft Matter. 2013;9:5516–5523.
  • Tajik A, Zhang Y, Wei F, et al. Transcription upregulation via force-induced direct stretching of chromatin. Nat Mater. 2016;15(12):1287–1296.
  • Elosegui-Artola A, Andreu I, Beedle AEM, et al. Force triggers YAP nuclear entry by regulating transport across nuclear pores. Cell. 2017;171:1397–410 e14.
  • Guilluy C, Osborne LD, Van Landeghem L, et al. Isolated nuclei adapt to force and reveal a mechanotransduction pathway in the nucleus. Nat Cell Biol. 2014;16(4):376–381.
  • Le HQ, Ghatak S, Yeung CY, et al. Mechanical regulation of transcription controls Polycomb-mediated gene silencing during lineage commitment. Nat Cell Biol. 2016;18:864–875.
  • Hatch EM, Hetzer MW. Nuclear envelope rupture is induced by actin-based nucleus confinement. J Cell Biol. 2016;215(1):27–36.
  • Zhang Q, Tamashunas AC, Agrawal A, et al. Local, transient tensile stress on the nuclear membrane causes membrane rupture. Mol Biol Cell. 2019;30(7):899–906.
  • Harada T, Swift J, Irianto J, et al. Nuclear lamin stiffness is a barrier to 3D migration, but softness can limit survival. J Cell Biol. 2014;204:669–682.
  • Rowat AC, Jaalouk DE, Zwerger M, et al. Nuclear envelope composition determines the ability of neutrophil-type cells to passage through micron-scale constrictions. J Biol Chem. 2013;288(12):8610–8618.
  • Wiggan O, Schroder B, Krapf D, et al. Cofilin regulates nuclear architecture through a myosin-II dependent mechanotransduction module. Sci Rep. 2017;7(1):40953.
  • Robijns J, Molenberghs F, Sieprath T, et al. In silico synchronization reveals regulators of nuclear ruptures in lamin A/C deficient model cells. Sci Rep. 2016;6(1):30325.
  • Thiam HR, Vargas P, Carpi N, et al. Perinuclear Arp2/3-driven actin polymerization enables nuclear deformation to facilitate cell migration through complex environments. Nat Commun. 2016;7:10997.
  • HiedaHM. Signal Transduction across the nuclear envelope: role of the LINC complex in bidirectional signaling. Cells. 2019;8 (2): 124.
  • Kutscheidt S, Zhu R, Antoku S, et al. FHOD1 interaction with nesprin-2G mediates TAN line formation and nuclear movement. Nat Cell Biol. 2014;16(7):708–715.
  • Antoku S, Zhu R, Kutscheidt S, et al. Reinforcing the LINC complex connection to actin filaments: the role of FHOD1 in TAN line formation and nuclear movement. Cell Cycle. 2015;14(14):2200–2205.
  • Jayo A, Malboubi M, Antoku S, et al. Fascin regulates nuclear movement and deformation in migrating cells. Dev Cell. 2016;38(4):371–383. DOI:10.1016/j.devcel.2016.07.021.
  • Saunders CA, Luxton GW. LINCing defective nuclear-cytoskeletal coupling and DYT1 dystonia. Cell Mol Bioeng. 2016;9(2):207–216.
  • Saunders CA, Harris NJ, Willey PT, et al. TorsinA controls TAN line assembly and the retrograde flow of dorsal perinuclear actin cables during rearward nuclear movement. J Cell Biol. 2017;216 (3):657–674.
  • Borrego-Pinto J, Jegou T, Osorio DS, et al. Samp1 is a component of TAN lines and is required for nuclear movement. J Cell Sci. 2012;125(5):1099–1105.
  • Thakar K, May CK, Rogers A, et al. Opposing roles for distinct LINC complexes in regulation of the small GTPase RhoA. Mol Biol Cell. 2017;28 (1):182–191.
  • Woroniuk A, Porter A, White G, et al. STEF/TIAM2-mediated Rac1 activity at the nuclear envelope regulates the perinuclear actin cap. Nat Commun. 2018;9(1):2124. DOI:10.1038/s41467-018-04404-4.
  • Kinugasa Y, Hirano Y, Sawai M, et al. The very-long-chain fatty acid elongase Elo2 rescues lethal defects associated with loss of the nuclear barrier function in fission yeast cells. J Cell Sci. 2019;132 (10):jcs229021.
  • Lusk CP, Ader NR. CHMPions of repair: emerging perspectives on sensing and repairing the nuclear envelope barrier. Curr Opin Cell Biol. 2020;64:25–33.
  • Jimenez AJ, Maiuri P, Lafaurie-Janvore J, et al. ESCRT machinery is required for plasma membrane repair. Science. 2014;343(6174):1247136.
  • Scheffer LL, Sreetama SC, Sharma N, et al. Mechanism of Ca(2)(+)-triggered ESCRT assembly and regulation of cell membrane repair. Nat Commun. 2014;5:5646.
  • Olmos Y, Hodgson L, Mantell J, et al. ESCRT-III controls nuclear envelope reformation. Nature. 2015;522(7555):236–239.
  • Olmos Y, Perdrix-Rosell A, Carlton JG. Membrane binding by CHMP7 coordinates ESCRT-III-dependent nuclear envelope reformation. Curr Biol. 2016;26(19):2635–2641.
  • Young AM, Gunn AL, Hatch EM. BAF facilitates interphase nuclear membrane repair through recruitment of nuclear transmembrane proteins. Mol Biol Cell. 2020;31(15):1551–1560.
  • Halfmann CT, Sears RM, Katiyar A, et al. Repair of nuclear ruptures requires barrier-to-autointegration factor. J Cell Biol. 2019;218(7):2136–2149.
  • Gorjanacz M, Klerkx EP, Galy V, et al. Caenorhabditis elegans BAF-1 and its kinase VRK-1 participate directly in post-mitotic nuclear envelope assembly. Embo J. 2007;26:132–143.
  • Haraguchi T, Koujin T, Segura-Totten M, et al. BAF is required for emerin assembly into the reforming nuclear envelope. J Cell Sci. 2001;114:4575–4585.
  • Haraguchi T, Kojidani T, Koujin T, et al. Live cell imaging and electron microscopy reveal dynamic processes of BAF-directed nuclear envelope assembly. J Cell Sci. 2008;121(15):2540–2554.
  • Samwer M, Schneider MWG, Hoefler R, Schmalhorst PS, Jude JG, Zuber J, Gerlich DW. DNA Cross-Bridging. Shapes a Single Nucleus from a Set of Mitotic Chromosomes. Cell. 2017;170:956–72 e23.
  • Huguet F, Flynn S, Vagnarelli P. The role of phosphatases in nuclear envelope disassembly and reassembly and their relevance to pathologies. Cells. 2019;8(7):687.
  • Kleinberger T. Biology of the adenovirus E4orf4 protein: from virus infection to cancer cell death. FEBS Lett. 2020;594(12):1891–1917.
  • Lavoie JN, Nguyen M, Marcellus RC, et al. E4orf4, a novel adenovirus death factor that induces p53-independent apoptosis by a pathway that is not inhibited by zVAD-fmk. J Cell Biol. 1998;140(3):637–645.
  • Shtrichman R, Sharf R, Barr H, et al. Induction of apoptosis by adenovirus E4orf4 protein is specific to transformed cells and requires an interaction with protein phosphatase 2A. Proc Natl Acad Sci U S A. 1999;96(18):10080–10085.
  • Marcellus RC, Lavoie JN, Boivin D, et al. The early region 4 orf4 protein of human adenovirus type 5 induces p53- independent cell death by apoptosis. J Virol. 1998;72(9):7144–7153.
  • Lavoie JN, Champagne C, Gingras MC, et al. Adenovirus E4 open reading frame 4-induced apoptosis involves dysregulation of src family kinases. J Cell Biol. 2000;150(5):1037–1056.
  • Lavoie JN, Landry MC, Faure RL, et al. Src-family kinase signaling, actin-mediated membrane trafficking and organellar dynamics in the control of cell fate: lessons to be learned from the adenovirus E4orf4 death factor. Cell Signal. 2010;22(11):1604–1614.
  • Robert A, Smadja-Lamere N, Landry MC, et al. Adenovirus E4orf4 hijacks rho GTPase-dependent actin dynamics to kill cells: a role for endosome-associated actin assembly. Mol Biol Cell. 2006;17(7):3329–3344.
  • Smadja-Lamere N, Boulanger MC, Champagne C, et al. JNK-mediated phosphorylation of paxillin in adhesion assembly and tension-induced cell death by the adenovirus death factor E4orf4. J Biol Chem. 2008;283(49):34352–34364.
  • Gingras M-C, Champagne C, Roy M, et al. Cytoplasmic death signal triggered by src-mediated phosphorylation of the Adenovirus E4orf4 protein. Mol Cell Biol. 2002;22(1):41–56.
  • Champagne C, Landry MC, Gingras MC, et al. Activation of adenovirus type 2 early region 4 ORF4 cytoplasmic death function by direct binding to Src kinase domain. J Biol Chem. 2004;279(24):25905–25915.
  • Landry MC, Sicotte A, Champagne C, et al. Regulation of cell death by recycling endosomes and golgi membrane dynamics via a pathway involving Src-family kinases, Cdc42 and Rab11a. Mol Biol Cell. 2009;20(18):4091–4106.
  • Landry MC, Champagne C, Boulanger MC, et al. A functional interplay between the small GTPase Rab11a and mitochondria-shaping proteins regulates mitochondrial positioning and polarization of the actin cytoskeleton downstream of src family kinases. J Biol Chem. 2014;289:2230–2249.
  • Dziengelewski C, Rodrigue MA, Caillier A, et al. Adenoviral protein E4orf4 interacts with the polarity protein Par3 to induce nuclear rupture and tumor cell death. J Cell Biol. 2020;219(4):e201805122.
  • Shtrichman R, Sharf R, Barr H, et al. Induction of apoptosis by adenovirus E4orf4 protein is specific to transformed cells and requires an interaction with protein phosphatase 2A. Proc Natl Acad Sci U S A. 1999;96(18):10080–10085.
  • Lele TP, Dickinson RB, Gundersen GG. Mechanical principles of nuclear shaping and positioning. J Cell Biol. 2018;217(10):3330–3342.
  • Irianto J, Xia Y, Pfeifer CR, et al. DNA damage follows repair factor depletion and portends genome variation in cancer cells after pore migration. Curr Biol. 2017;27(2):210–223.
  • Rosen H, Sharf R, Pechkovsky A, et al. Selective elimination of cancer cells by the adenovirus E4orf4 protein in a Drosophila cancer model: a new paradigm for cancer therapy. Cell Death Dis. 2019;10(6):455.
  • Mui MZ, Zhou Y, Blanchette P, et al. The Human Adenovirus Type 5 E4orf4 Protein Targets Two Phosphatase Regulators of the Hippo Signaling Pathway. J Virol. 2015;89(17):8855–8870.
  • Lu Y, Kucharski TJ, Gamache I, et al. Interaction of adenovirus type 5 E4orf4 with the nuclear pore subunit Nup205 is required for proper viral gene expression. J Virol. 2014;88(22):13249–13259.
  • Ferrigno P, Langan TA, Cohen P. Protein phosphatase 2A1 is the major enzyme in vertebrate cell extracts that dephosphorylates several physiological substrates for cyclin-dependent protein kinases. Mol Biol Cell. 1993;4(7):669–677.
  • Virshup DM, Shenolikar S. From promiscuity to precision: protein phosphatases get a makeover. Mol Cell. 2009;33(5):537–545.
  • Lang CF, Munro E. The PAR proteins: from molecular circuits to dynamic self-stabilizing cell polarity. Development. 2017;144(19):3405–3416.
  • Goldstein B, Macara IG. The PAR proteins: fundamental players in animal cell polarization. Dev Cell. 2007;13(5):609–622.
  • Nance J, Zallen JA. Elaborating polarity: PAR proteins and the cytoskeleton. Development. 2011;138(5):799–809.
  • Mack NA, Georgiou M. The interdependence of the Rho GTPases and apicobasal cell polarity. Small GTPases. 2014;5(2):10.
  • Munro E. Protein Clustering Shapes Polarity Protein Gradients. Dev Cell. 2017;42(4):309–311.
  • Grassie ME, Moffat LD, Walsh MP, et al. The myosin phosphatase targeting protein (MYPT) family: a regulated mechanism for achieving substrate specificity of the catalytic subunit of protein phosphatase type 1delta. Arch Biochem Biophys. 2011;510:147–159.
  • Kiss A, Erdodi F, Lontay B. Myosin phosphatase: unexpected functions of a long-known enzyme. Biochim Biophys Acta Mol Cell Res. 2019;1866(1):2–15.
  • Fehon RG, McClatchey AI, Bretscher A. Organizing the cell cortex: the role of ERM proteins. Nat Rev Mol Cell Biol. 2010;11:276–287.
  • Kiss A, Lontay B, Becsi B, et al. Myosin phosphatase interacts with and dephosphorylates the retinoblastoma protein in THP-1 leukemic cells: its inhibition is involved in the attenuation of daunorubicin-induced cell death by calyculin-A. Cell Signal. 2008;20:2059–2070.
  • Bergamaschi D, Samuels Y, Jin B, et al. ASPP1 and ASPP2: common activators of p53 family members. Mol Cell Biol. 2004;24(3):1341–1350.
  • Liu CY, Lv X, Li T, et al. PP1 cooperates with ASPP2 to dephosphorylate and activate TAZ. J Biol Chem. 2011;286:5558–5566.
  • Royer C, Koch S, Qin X, et al. ASPP2 links the apical lateral polarity complex to the regulation of YAP activity in epithelial cells. PloS One. 2014;9:e111384.
  • Wang W, Li X, Huang J, et al. Defining the protein-protein interaction network of the human hippo pathway. Mol Cell Proteomics. 2014;13(1):119–131.
  • Moya IM, Halder G. Discovering the Hippo pathway protein-protein interactome. Cell Res. 2014;24(2):137–138.
  • Zheng X, Dong Q, Zhang X, et al. The coiled-coil domain of oncogene RASSF 7 inhibits hippo signaling and promotes non-small cell lung cancer. Oncotarget. 2017;8:78734–78748.
  • Couzens AL, Knight JD, Kean MJ, et al. Protein interaction network of the mammalian Hippo pathway reveals mechanisms of kinase-phosphatase interactions. Sci Signal. 2013;6:rs15.
  • Cong W, Hirose T, Harita Y, et al. ASPP2 regulates epithelial cell polarity through the PAR complex. Curr Biol. 2010;20(15):1408–1414.
  • Sottocornola R, Royer C, Vives V, et al. ASPP2 binds Par-3 and controls the polarity and proliferation of neural progenitors during CNS development. Dev Cell. 2010;19(1):126–137. DOI:10.1016/j.devcel.2010.06.003.
  • Langton PF, Colombani J, Chan EH, et al. The dASPP-dRASSF8 complex regulates cell-cell adhesion during Drosophila retinal morphogenesis. Curr Biol. 2009;19(23):1969–1978.
  • Wang Y, Bu F, Royer C, et al. ASPP2 controls epithelial plasticity and inhibits metastasis through beta-catenin-dependent regulation of ZEB1. Nat Cell Biol. 2014;16(11):1092–1104.
  • Bertran MT, Mouilleron S, Zhou Y, et al. ASPP proteins discriminate between PP1 catalytic subunits through their SH3 domain and the PP1 C-tail. Nat Commun. 2019;10(1):771.
  • Kleinberger T, Shenk T. Adenovirus E4orf4 protein binds to protein phosphatase 2A, and the complex down regulates E1A-enhanced junB transcription. J Virol. 1993;67(12):7556–7560.
  • Marcellus RC, Chan H, Paquette D, et al. Induction of p53-independent apoptosis by the adenovirus E4orf4 protein requires binding to the Balpha subunit of protein phosphatase 2A. J Virol. 2000;74(17):7869–7877.
  • Roopchand DE, Lee JM, Shahinian S, et al. Toxicity of human adenovirus E4orf4 protein in Saccharomyces cerevisiae results from interactions with the Cdc55 regulatory B subunit of PP2A. Oncogene. 2001;20(38):5279–5290.
  • Kanopka A, Muhlemann O, Petersen-Mahrt S, et al. Regulation of adenovirus alternative RNA splicing by dephosphorylation of SR proteins. Nature. 1998;393(6681):185–187.
  • Estmer Nilsson C, Petersen-Mahrt S, Durot C, et al. The adenovirus E4-ORF4 splicing enhancer protein interacts with a subset of phosphorylated SR proteins. EMBO J. 2001;20(4):864–871.
  • 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.
  • Schmitz MH, Held M, Janssens V, et al. Live-cell imaging RNAi screen identifies PP2A-B55alpha and importin-beta1 as key mitotic exit regulators in human cells. Nat Cell Biol. 2010;12(9):886–893.
  • Snyers L, Erhart R, Laffer S, et al. LEM4/ANKLE-2 deficiency impairs post-mitotic re-localization of BAF, LAP2alpha and LaminA to the nucleus, causes nuclear envelope instability in telophase and leads to hyperploidy in HeLa cells. Eur J Cell Biol. 2018;97:63–74.
  • Mehsen H, Boudreau V, Garrido D, et al. PP2A-B55 promotes nuclear envelope reformation after mitosis in Drosophila. J Cell Biol. 2018;217(12):4106–4123.
  • Asencio C, Davidson IF, Santarella-Mellwig R, et al. Coordination of kinase and phosphatase activities by Lem4 enables nuclear envelope reassembly during mitosis. Cell. 2012;150(1):122–135.
  • Mazumder A, Roopa T, Basu A, et al. Dynamics of chromatin decondensation reveals the structural integrity of a mechanically prestressed nucleus. Biophys J. 2008;95(6):3028–3035.
  • Krause M, Yang FW, Te Lindert M, et al. Cell migration through three-dimensional confining pores: speed accelerations by deformation and recoil of the nucleus. Philos Trans R Soc London, Ser B. 2019;374:20180225.
  • Brestovitsky A, Sharf R, Mittelman K, et al. The adenovirus E4orf4 protein targets PP2A to the ACF chromatin-remodeling factor and induces cell death through regulation of SNF2h-containing complexes. Nucleic Acids Res. 2011;39(15):6414–6427.
  • Fyodorov DV, Blower MD, Karpen GH, et al. Acf1 confers unique activities to ACF/CHRAC and promotes the formation rather than disruption of chromatin in vivo. Genes Dev. 2004;18(2):170–183.
  • Machida S, Takizawa Y, Ishimaru M, et al. Structural Basis of Heterochromatin Formation by Human HP1. Mol Cell. 2018;69(3):385–397 e8.
  • Bertacchini J, Beretti F, Cenni V, et al. The protein kinase Akt/PKB regulates both prelamin A degradation and Lmna gene expression. FASEB J. 2013;27(6):2145–2155.
  • Loie E, Charrier LE, Sollier K, et al. CRB3A Controls the morphology and cohesion of cancer cells through Ehm2/p114RhoGEF-dependent signaling. Mol Cell Biol. 2015;35(19):3423–3435.
  • Hirano M, Hashimoto S, Yonemura S, et al. EPB41L5 functions to post-transcriptionally regulate cadherin and integrin during epithelial-mesenchymal transition. J Cell Biol. 2008;182(6):1217–1230.
  • Fabregat A, Sidiropoulos K, Viteri G, et al. Reactome pathway analysis: a high-performance in-memory approach. BMC Bioinformatics. 2017;18(1):142.
  • Grallert A, Boke E, Hagting A, et al. A PP1-PP2A phosphatase relay controls mitotic progression. Nature. 2015;517:94–98.
  • Jamin A, Wiebe MS. Barrier to Autointegration Factor (BANF1): interwoven roles in nuclear structure, genome integrity, innate immunity, stress responses and progeria. Curr Opin Cell Biol. 2015;34:61–68.
  • Luxton GW, Gomes ER, Folker ES, et al. TAN lines: a novel nuclear envelope structure involved in nuclear positioning. Nucleus. 2011;2(3):173–181.
  • Kim DH, Khatau SB, Feng Y, et al. Actin cap associated focal adhesions and their distinct role in cellular mechanosensing. Sci Rep. 2012;2:555.
  • Choi H, Larsen B, Lin ZY, et al. SAINT: probabilistic scoring of affinity purification-mass spectrometry data. Nat Methods. 2011;8:70–73.
  • Choi H, Liu G, Mellacheruvu D, et al. Analyzing protein-protein interactions from affinity purification-mass spectrometry data with SAINT. Curr Protoc Bioinformatics. 2012;Chapter 8: Unit8.15.
  • The UniProt C. UniProt: the universal protein knowledgebase. Nucleic Acids Res. 2017;45:D158–D69.
  • Shannon P, Markiel A, Ozier O, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498–2504.
  • Jassal B, Matthews L, Viteri G, et al. The reactome pathway knowledgebase. Nucleic Acids Res. 2020;48:D498–D503.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.