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Hexim1, an RNA-controlled protein hub

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Pages 262-271 | Received 27 Nov 2017, Accepted 15 Jan 2018, Published online: 23 Feb 2018

References

  • Kusuhara M, Nagasaki K, Kimura K, et al. Cloning of hexamethylene-bis-acetamide-inducible transcript, HEXIM1, in human vascular smooth muscle cells. Biomed Res. 1999;20:273–279. doi:10.2220/biomedres.20.273.
  • Ghatpande S, Goswami S, Mathew S, et al. Identification of a novel cardiac lineage-associated protein(cCLP-1): a candidate regulator of cardiogenesis. Dev Biol. 1999;208:210–221. doi:10.1006/dbio.1998.9180. PMID:10075853
  • Michels AA, Nguyen VT, Fraldi A, et al. MAQ1 and 7SK RNA interact with CDK9/cyclin T complexes in a transcription-dependent manner. Mol Cell Biol. 2003;23(14):4859–4869. doi:10.1128/MCB.23.14.4859-4869.2003. PMID:12832472
  • Wittmann BM, Wang N, Montano MM. Identification of a novel inhibitor of breast cell growth that is down-regulated by estrogens and decreased in breast tumors. Cancer Res. 2003;63(16):5151–5158. PMID:12941847
  • Ketchart W, Yeh IJ, Zhou H, et al. Induction of HEXIM1 activities by HMBA derivative 4a1: functional consequences and mechanism. Cancer Lett. 2016;379(1):60–69. doi:10.1016/j.canlet.2016.05.029. PMID:27238569
  • Liu P, Xiang Y, Fujinaga K, et al. Release of positive transcription elongation factor b (P-TEFb) from 7SK small nuclear ribonucleoprotein (snRNP) activates hexamethylene bisacetamide-inducible protein (HEXIM1) transcription. J Biol Chem. 2014;289(14):9918–9925. doi:10.1074/jbc.M113.539015. PMID:24515107
  • Tan JL, Zhao Q, Liang X, et al. Stress from nucleotide depletion activates the transcriptional regulator HEXIM1 to suppress melanoma. Mol Cell. 2016;62(1):34–46. doi:10.1016/j.molcel.2016.03.013. PMID:27058786
  • Han L, Zhao Q, Liang X, et al. Ubenimex enhances Brd4 inhibition by suppressing HEXIM1 autophagic degradation and suppressing the Akt pathway in glioma cells. Oncotarget. 2017;8(28):45643–45655. doi:10.18632/oncotarget.17314. PMID:28484091
  • Marz M, Donath A, Verstraete N, et al. Evolution of 7SK RNA and its protein partners in metazoa. Mol Biol Evol. 2009;26:2821–2830. doi:10.1093/molbev/msp198. PMID:19734296
  • Nguyen D, Fayol O, Buisine N, et al. Functional interaction between HEXIM and hedgehog signaling during drosophila wing development. PLoS One. 2016;11(5):e0155438. doi:10.1371/journal.pone.0155438. PMID:27176767
  • Huang F, Wagner M, Siddiqui MA. Ablation of the CLP-1 gene leads to down-regulation of the HAND1 gene and abnormality of the left ventricle of the heart and fetal death. Mech Dev. 2004;121(6):559–572. doi:10.1016/j.mod.2004.04.012. PMID:15172687
  • Yik JH, Chen R, Pezda AC, et al. Compensatory contributions of HEXIM1 and HEXIM2 in maintaining the balance of active and inactive P-TEFb complexes for control of transcription. J Biol Chem. 2005;280:16368–16376. doi:10.1074/jbc.M500912200. PMID:15713661
  • Czudnochowski N, Vollmuth F, Baumann S, et al. Specificity of Hexim1 and Hexim2 complex formation with cyclin T1/T2, importin alpha and 7SK snRNA. J Mol Biol. 2010;395(1):28–41. doi:10.1016/j.jmb.2009.10.055. PMID:19883659
  • Badrock A, Hurlstone A. A hexIM1 on your melanocytes: transcription elongation – the Achilles' heel of melanoma? Pigment Cell Melanoma Res. 2016;29(5):496–497. doi:10.1111/pcmr.12509. PMID:27399276
  • Chen R, Yik JH, Lew QJ, et al. Brd4 and HEXIM1: multiple roles in P-TEFb regulation and cancer. Biomed Res Int. 2014;2014:232870. PMID:24592384
  • Catalucci D, Condorelli G. HEXIM1: a new player in myocardial hypertrophy? Cardiovasc Res. 2013;99(1):1–3. doi:10.1093/cvr/cvt134. PMID:23720275
  • Dey A, Chao SH, Lane DP. HEXIM1 and the control of transcription elongation: from cancer and inflammation to AIDS and cardiac hypertrophy. Cell Cycle. 2007;6(15):1856–1863. doi:10.4161/cc.6.15.4556. PMID:17671421
  • Asakura A. Vascular endothelial growth factor gene regulation by HEXIM1 in heart. Circ Res. 2008;102(4):398–400. doi:10.1161/CIRCRESAHA.108.172114. PMID:18309107
  • Yik JH, Chen R, Pezda AC, et al. A human immunodeficiency virus type 1 Tat-like arginine-rich RNA-binding domain is essential for HEXIM1 to inhibit RNA polymerase II transcription through 7SK snRNA-mediated inactivation of P-TEFb. Mol Cell Biol. 2004;24(12):5094–5105. doi:10.1128/MCB.24.12.5094-5105.2004. PMID:15169877
  • Michels AA, Fraldi A, Li Q, et al. Binding of the 7SK snRNA turns the HEXIM1 protein into a P-TEFb (CDK9/cyclin T) inhibitor. Embo J. 2004;23(13):2608–2619. doi:10.1038/sj.emboj.7600275. PMID:15201869
  • Barboric M, Kohoutek J, Price JP, et al. Interplay between 7SK snRNA and oppositely charged regions in HEXIM1 direct the inhibition of P-TEFb. Embo J. 2005;24(24):4291–4303. doi:10.1038/sj.emboj.7600883. PMID:16362050
  • Biglione S, Byers SA, Price JP, et al. Inhibition of HIV-1 replication by P-TEFb inhibitors DRB, seliciclib and flavopiridol correlates with release of free P-TEFb from the large, inactive form of the complex. Retrovirology. 2007;4:47. doi:10.1186/1742-4690-4-47. PMID:17625008
  • Dames SA, Schönichen A, Schulte A, et al. Structure of the Cyclin T binding domain of Hexim1 and molecular basis for its recognition of P-TEFb. Proc Natl Acad Sci U S A. 2007;104:14312–14317. doi:10.1073/pnas.0701848104. PMID:17724342
  • Schonichen A, Bigalke JM, Urbanke C, et al. A flexible bipartite coiled coil structure is required for the interaction of Hexim1 with the P-TEFB subunit cyclin T1. Biochemistry. 2010;49:3083–3091. doi:10.1021/bi902072f. PMID:20210365
  • Byers SA, Price JP, Cooper JJ, et al. HEXIM2, A HEXIM1 related protein, regulates P-TEFb through association with 7SK. J Biol Chem. 2005;280:16360–16367. doi:10.1074/jbc.M500424200. PMID:15713662
  • Li Q, Price JP, Byers SA, et al. Analysis of the large inactive P-TEFb complex indicates that it contains one 7SK molecule, a dimer of HEXIM1 or HEXIM2, and two P-TEFb molecules containing Cdk9 phosphorylated at threonine 186. J Biol Chem. 2005;280:28819–28826. doi:10.1074/jbc.M502712200. PMID:15965233
  • Dulac C, Michels AA, Fraldi A, et al. Transcription-dependent association of multiple P-TEFb units to a HEXIM multimer. J Biol Chem. 2005;280:30619–30629. doi:10.1074/jbc.M502471200. PMID:15994294
  • Mitrea DM, Yoon MK, Ou L, et al. Disorder-function relationships for the cell cycle regulatory proteins p21 and p27. Biol Chem. 2012;393(4):259–274. doi:10.1515/hsz-2011-0254. PMID:23029651
  • Zhou Q, Li T, Price DH. RNA Polymerase II Elongation Control. Annu Rev Biochem. 2012;81:119–143. doi:10.1146/annurev-biochem-052610-095910. PMID:22404626
  • Jonkers I, Lis JT. Getting up to speed with transcription elongation by RNA polymerase II. Nat Rev Mol Cell Biol. 2015;16(3):167–177. doi:10.1038/nrm3953. PMID:25693130
  • Li Y, Liu M, Chen LF, et al. P-TEFb: finding its ways to release promoter-proximally paused RNA Polymerase II. Transcription. 2017;19:1–7. doi:10.1080/21541264.2017.1281864.
  • Diribarne G, Bensaude O. 7SK RNA, a non-coding RNA regulating P-TEFb, a general transcription factor. RNA Biol. 2009;6:122–128. doi:10.4161/rna.6.2.8115. PMID:19246988
  • McNamara RP, Bacon CW, D'Orso I. Transcription elongation control by the 7SK snRNP complex: releasing the pause. Cell Cycle. 2016;15(16):2115–2123. doi:10.1080/15384101.2016.1181241. PMID:27152730
  • Quaresma AJ, Bugai A, Barboric M. Cracking the control of RNA polymerase II elongation by 7SK snRNP and P-TEFb. Nucleic Acids Res. 2016;44(16):7527–7539. doi:10.1093/nar/gkw585. PMID:27369380
  • Nguyen D, Krueger BJ, Sedore SC, et al. The Drosophila 7SK snRNP and the essential role of dHEXIM in development. Nucleic Acids Res. 2012;40(12):5283–5297. doi:10.1093/nar/gks191.
  • Verstraete N, Kuzmina A, Diribarne G, et al. A cyclin T1 point mutation that abolishes positive transcription elongation factor (P-TEFb) binding to HEXIM1 and HIV tat. Retrovirology. 2014;11(50): doi:10.1186/1742-4690-11-50.
  • Egloff S, Van Herreweghe E, Kiss T. Regulation of polymerase II transcription by 7SK snRNA: two distinct RNA elements direct P-TEFb and HEXIM1 binding. Mol Cell Biol. 2006;26(2):630–642. doi:10.1128/MCB.26.2.630-642.2006. PMID:16382153
  • Martinez-Zapien D, Saliou JM, Han X, et al. Intermolecular recognition of the non-coding RNA 7SK and HEXIM protein in perspective. Biochimie. 2015;117:63–71. doi:10.1016/j.biochi.2015.03.020. PMID:25863285
  • Brogie JE, Price DH. Reconstitution of a functional 7SK snRNP. Nucleic Acids Res. 2017;45(11):6864–6880. doi:10.1093/nar/gkx262. PMID:28431135
  • Lebars I, Martinez-Zapien D, Durand A, et al. HEXIM1 targets a repeated GAUC motif in the riboregulator of transcription 7SK and promotes base pair rearrangements. Nucleic Acids Res. 2010;38:7749–7763. doi:10.1093/nar/gkq660. PMID:20675720
  • Martinez-Zapien D, Legrand P, McEwen AG, et al. The crystal structure of the 5 functional domain of the transcription riboregulator 7SK. Nucleic Acids Res. 2017;45(6):3568–3579. PMID:28082395
  • Fujinaga K, Luo Z, Peterlin BM. Genetic analysis of the structure and function of 7SK small nuclear ribonucleoprotein (snRNP) in cells. J Biol Chem. 2014;289(30):21181–21190. doi:10.1074/jbc.M114.557751. PMID:24917669
  • Bélanger F, Baigude H, Rana TM. U30 of 7SK RNA Forms a Specific Photo-cross-link with Hexim1 in the Context of Both a Minimal RNA-binding,site and a Fully Reconstituted 7SK/Hexim1/P-TEFb,Ribonucleoprotein Complex. J Mol Biol. 2009;386:1094–1107. doi:10.1016/j.jmb.2009.01.015. PMID:19244621
  • Czudnochowski N, Bosken CA, Geyer M. Serine-7 but not serine-5 phosphorylation primes RNA polymerase II CTD for P-TEFb recognition. Nat Commun. 2012;3:842. doi:10.1038/ncomms1846. PMID:22588304
  • Schulte A, Czudnochowski N, Barboric M, et al. Identification of a cyclin T-binding domain in Hexim1 and biochemical analysis of its binding competition with HIV-1 Tat. J Biol Chem. 2005;280:24968–24977. doi:10.1074/jbc.M501431200. PMID:15855166
  • Ogba N, Doughman YQ, Chaplin LJ, et al. HEXIM1 modulates vascular endothelial growth factor expression and function in breast epithelial cells and mammary gland. Oncogene. 2010;29:3639–3649. doi:10.1038/onc.2010.110. PMID:20453883
  • Kobbi L, Demey-Thomas E, Braye F, et al. An evolutionary conserved Hexim1 peptide binds to the Cdk9 catalytic site to inhibit P-TEFb. Proc Natl Acad Sci USA. 2016; 201612331. doi:10.1073/pnas.1612331113. PMID:27791144
  • Chen R, Yang Z, Zhou Q. Phosphorylated P-TEFb is tagged for inhibition through association with 7SK snRNA. J Biol Chem. 2004;279:4153–4160. doi:10.1074/jbc.M310044200. PMID:14627702
  • Ott M, Geyer M, Zhou Q. The control of HIV transcription: keeping RNA polymerase II on track. Cell Host Microbe. 2011;10(5):426–435. doi:10.1016/j.chom.2011.11.002. PMID:22100159
  • Tahirov TH, Babayeva ND, Varzavand K, et al. Crystal structure of HIV-1 Tat complexed with human P-TEFb. Nature. 2010;465:747–751. doi:10.1038/nature09131. PMID:20535204
  • Sedore SC, Byers SA, Biglione S, et al. Manipulation of P-TEFb control machinery by HIV: recruitment of P-TEFb from the large form by Tat and binding of HEXIM1 to TAR. Nucleic Acids Res. 2007;35:4347–4358. doi:10.1093/nar/gkm443. PMID:17576689
  • Li Q, Cooper JJ, Altwerger GH, et al. HEXIM1 is a promiscuous double-stranded RNA-binding protein and interacts with RNAs in addition to 7SK in cultured cells. Nucleic Acids Res. 2007;35:2503–2512. doi:10.1093/nar/gkm150. PMID:17395637
  • D'Orso I, Jang GM, Pastuszak AW, et al. Transition step during assembly of HIV Tat:P-TEFb transcription complexes and transfer to TAR RNA. Mol Cell Biol. 2012;32(23):4780–4793. doi:10.1128/MCB.00206-12. PMID:23007159
  • Mizutani T, Ishizaka A, Suzuki Y, et al. 7SK small nuclear ribonucleoprotein complex is recruited to the HIV-1 promoter via short viral transcripts. FEBS Lett. 2014;588(9):1630–1636. doi:10.1016/j.febslet.2014.01.067. PMID:24607481
  • Barboric M, Yik JH, Czudnochowski N, et al. Tat competes with HEXIM1 to increase the active pool of P-TEFb for HIV-1 transcription. Nucleic Acids Res. 2007;35:2003–2012. doi:10.1093/nar/gkm063. PMID:17341462
  • Fraldi A, Varrone F, Napolitano G, et al. Inhibition of Tat activity by the HEXIM1 protein. Retrovirology. 2005;2(1):42. doi:10.1186/1742-4690-2-42. PMID:15992410
  • Muck F, Bracharz S, Marschalek R. DDX6 transfers P-TEFb kinase to the AF4/AF4N (AFF1) super elongation complex. Am J Blood Res. 2016;6(3):28–45. PMID:27679741
  • Nguyen VT, Kiss T, Michels AA, et al. 7SK snRNA binds to and inhibits the activity of Cdk9/cyclin T complexes. Nature. 2001;414:322–325. doi:10.1038/35104581. PMID:11713533
  • Yang Z, Zhu Q, Luo K, et al. The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription. Nature. 2001;414:317–322. doi:10.1038/35104575. PMID:11713532
  • Barrandon C, Bonnet F, Nguyen VT, et al. The transcription-dependent dissociation of P-TEFb.HEXIM1.7SK RNA relies upon formation of hnRNP.7SK RNA complexes. Mol Cell Biol. 2007;27:6996–7006. doi:10.1128/MCB.00975-07. PMID:17709395
  • Van Herreweghe E, Egloff S, Goiffon I, et al. Dynamic remodelling of human 7SK snRNP controls the nuclear level of active P-TEFb. EMBO J. 2007;26(15):3570–3580. doi:10.1038/sj.emboj.7601783. PMID:17611602
  • Lemieux B, Blanchette M, Monette A, et al. A Function for the hnRNP A1/A2 proteins in transcription elongation. PLoS One. 2015;10(5):e0126654. doi:10.1371/journal.pone.0126654. PMID:26011126
  • Contreras X, Barboric M, Lenasi T, et al. HMBA releases P-TEFb from HEXIM1 and 7SK snRNA via PI3K/Akt and activates HIV transcription. PLoS Pathog. 2007;3(10):1459–1469. doi:10.1371/journal.ppat.0030146. PMID:17937499
  • Mbonye UR, Wang B, Gokulrangan G, et al. Phosphorylation of HEXIM1 at Tyr271 and Tyr274 Promotes Release of P-TEFb from the 7SK snRNP Complex and Enhances Proviral HIV Gene Expression. Proteomics. 2015;15(12):2078–2086. doi:10.1002/pmic.201500038. PMID:25900325
  • Kim YK, Mbonye U, Hokello J, et al. T-cell receptor signaling enhances transcriptional elongation from latent HIV proviruses by activating P-TEFb through an ERK-dependent pathway. J Mol Biol. 2011;410:896–916. doi:10.1016/j.jmb.2011.03.054. PMID:21763495
  • Fujinaga K, Barboric M, Li Q, et al. PKC phosphorylates HEXIM1 and regulates P-TEFb activity. Nucleic Acids Res. 2012;40(18):9160–9170. doi:10.1093/nar/gks682. PMID:22821562
  • Espinoza-Derout J, Wagner M, Shahmiri K, et al. Pivotal role of cardiac lineage protein-1 (CLP-1) in transcriptional elongation factor P-TEFb complex formation in cardiac hypertrophy. Cardiovasc Res. 2007;75:129–138. doi:10.1016/j.cardiores.2007.03.019. PMID:17459355
  • Chen R, Liu M, Li H, et al. PP2B and PP1cooperatively disrupt 7SK snRNP to release P-TEFb for transcription in response to Ca 2+ signaling Genes Dev. 2008;22:1356–1368. doi:10.1101/gad.1636008. PMID:18483222
  • Wang Y, Dow EC, Liang YY, et al. Phosphatase PPM1A regulates phosphorylation of Thr-186 in the Cdk9 T-loop. J Biol Chem. 2008;283(48):33578–33584. doi:10.1074/jbc.M807495200. PMID:18829461
  • Gudipaty SA, D'Orso I. Functional interplay between PPM1G and the transcription elongation machinery. RNA Dis. 2016;3(1): PMID:27088130
  • Zhang H, Park SH, Pantazides BG, et al. SIRT2 directs the replication stress response through CDK9 deacetylation. Proc Natl Acad Sci USA. 2013;110(33):13546–13551. doi:10.1073/pnas.1301463110. PMID:23898190
  • Blank MF, Chen S, Poetz F, et al. SIRT7-dependent deacetylation of CDK9 activates RNA polymerase II transcription. Nucleic Acids Res. 2017;45(5):2675–2686. doi:10.1093/nar/gkx053. PMID:28426094
  • Galatioto J, Mascareno E, Siddiqui MA. CLP-1 associates with MyoD and HDAC to restore skeletal muscle cell regeneration. J Cell Sci. 2010;123(Pt 21):3789–3795. doi:10.1242/jcs.073387. PMID:20940258
  • McNamara RP, McCann JL, Gudipaty SA, et al. Transcription factors mediate the enzymatic disassembly of promoter-bound 7SK snRNP to locally recruit P-TEFb for transcription elongation. Cell Rep. 2013;5:1256–1268. doi:10.1016/j.celrep.2013.11.003. PMID:24316072
  • Gudipaty SA, McNamara RP, Morton EL, et al. PPM1G binds 7SK RNA and Hexim1 to block P-TEFb assembly into the 7SK snRNP and sustain transcription elongation. Mol Cell Biol. 2015;35(22):3810–3828. doi:10.1128/MCB.00226-15. PMID:26324325
  • D'Orso I. 7SKiing on chromatin: move globally, act locally. RNA Biol. 2016;13(6):545–553. doi:10.1080/15476286.2016.1181254. PMID:27128603
  • Ji X, Zhou Y, Pandit S, et al. SR proteins collaborate with 7SK and promoter-associated nascent RNA to release paused polymerase. Cell. 2013;153(4):855–868. doi:10.1016/j.cell.2013.04.028. PMID:23663783
  • Ouchida R, Kusuhara M, Shimizu N, et al. Suppression of NF-kappaB-dependent gene expression by a hexamethylene bisacetamide-inducible protein HEXIM1 in human vascular smooth muscle cells. Genes Cells. 2003;8(2):95–107. doi:10.1046/j.1365-2443.2003.00618.x. PMID:12581153
  • Ketchart W, Ogba N, Kresak A, et al. HEXIM1 is a critical determinant of the response to tamoxifen. Oncogene. 2011;30:3563–3569. doi:10.1038/onc.2011.76. PMID:21423213
  • Wittmann BM, Fujinaga K, Deng H, et al. The breast cell growth inhibitor, estrogen down regulated gene 1, modulates a novel functional interaction between estrogen receptor alpha and transcriptional elongation factor cyclin T1. Oncogene. 2005;24: doi:10.1038/sj.onc.1208728. PMID:15940264
  • Yeh IJ, Song K, Wittmann BM, et al. HEXIM1 plays a critical role in the inhibition of the androgen receptor by anti-androgens. Biochem J. 2014;462(2):315–327. doi:10.1042/BJ20140174. PMID:24844355
  • Shimizu N, Ouchida R, Yoshikawa N, et al. HEXIM1 forms a transcriptionally abortive complex with glucocorticoid receptor without involving 7SK RNA and positive transcription elongation factor b. Proc Natl Acad Sci USA. 2005;102:8555–8560. doi:10.1073/pnas.0409863102. PMID:15941832
  • Liu X, Gao Y, Ye H, et al. Positive feedback loop mediated by protein phosphatase 1alpha mobilization of P-TEFb and basal CDK1 drives androgen receptor in prostate cancer. Nucleic Acids Res. 2017;45(7):3738–3751. PMID:28062857
  • Lama R, Gan C, Idippily N, et al. HMBA is a putative HSP70 activator stimulating HEXIM1 expression that is down-regulated by estrogen. J Steroid Biochem Mol Biol. 2017;168:91–101. doi:10.1016/j.jsbmb.2017.02.008. PMID:28213333
  • Kanno T, Kanno Y, LeRoy G, et al. BRD4 assists elongation of both coding and enhancer RNAs by interacting with acetylated histones. Nat Struct Mol Biol. 2014;21(12):1047–1057. doi:10.1038/nsmb.2912.
  • Winter GE, Mayer A, Buckley DL, et al. BET bromodomain proteins function as master transcription elongation factors independent of CDK9 recruitment. Mol Cell. 2017;67(1):5–18, e19. doi:10.1016/j.molcel.2017.06.004. PMID:28673542
  • Schroder S, Cho S, Zeng L, et al. Two-pronged binding with bromodomain-containing protein 4 liberates positive transcription elongation factor b from inactive ribonucleoprotein complexes. J Biol Chem. 2012;287(2):1090–1099. doi:10.1074/jbc.M111.282855. PMID:22084242
  • Itzen F, Greifenberg AK, Bosken CA, et al. Brd4 activates P-TEFb for RNA polymerase II CTD phosphorylation. Nucleic Acids Res. 2014;42(12):7577–7590. doi:10.1093/nar/gku449. PMID:24860166
  • Liu L, Xu Y, He M, et al. Transcriptional pause release is a rate-limiting step for somatic cell reprogramming. Cell Stem Cell. 2014;15(5):574–588. doi:10.1016/j.stem.2014.09.018. PMID:25312495
  • Egloff S, Studniarek C, Kiss T. 7SK small nuclear RNA, a multifunctional transcriptional regulatory RNA with gene-specific features. Transcription. 2017;18:1–7. doi:10.1080/21541264.2017.1344346.
  • Gurumurthy M, Tan CH, Ng R, et al. Nucleophosmin interacts with HEXIM1 and regulates RNA polymerase II transcription. J Mol Biol.2008;378(2):302–317. doi:10.1016/j.jmb.2008.02.055. PMID:18371977
  • Lew QJ, Chu KL, Chia YL, et al. HEXIM1, a New Player in the p53 Pathway. Cancers (Basel). 2013;5(3):838–856. doi:10.3390/cancers5030838. PMID:24202322
  • Yeh IJ, Ogba N, Bensigner H, et al. HEXIM1 down-regulates hypoxia-inducible factor-1alpha protein stability. Biochem J. 2013;456(2):195–204. doi:10.1042/BJ20130592. PMID:24015760
  • Fujimoto Y, Nakamura Y, Ohuchi S. HEXIM1-binding elements on mRNAs identified through transcriptomic SELEX and computational screening. Biochimie. 2012;94(9):1900–1909. doi:10.1016/j.biochi.2012.05.003. PMID:22609015
  • Morchikh M, Cribier A, Raffel R, et al. HEXIM1 and NEAT1 Long Non-coding RNA form a multi-subunit complex that regulates DNA-mediated innate immune response. Mol Cell. 2017;67:387–399. doi:10.1016/j.molcel.2017.06.020. PMID:28712728
  • Adriaens C, Marine JC. NEAT1-containing paraspeckles: Central hubs in stress response and tumor formation. Cell Cycle. 2017;16(2):137–138. doi:10.1080/15384101.2016.1235847. PMID:27700225
  • Kato K, Omura H, Ishitani R, et al. Cyclic GMP-AMP as an endogenous second messenger in innate immune signaling by cytosolic DNA. Annu Rev Biochem. 2017;86:541–566. doi:10.1146/annurev-biochem-061516-044813. PMID:28399655

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