USP44 positively regulates innate immune response to DNA viruses through deubiquitinating MITA
Autoři:
Hong-Yan Zhang aff001; Bo-Wei Liao aff001; Zhi-Sheng Xu aff001; Yong Ran aff001; Dong-Peng Wang aff001; Yan Yang aff001; Wei-Wei Luo aff001; Yan-Yi Wang aff001
Působiště autorů:
Key Laboratory of Special Pathogens and Biosafety, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China
aff001; University of Chinese Academy of Sciences, Beijing, China
aff002
Vyšlo v časopise:
USP44 positively regulates innate immune response to DNA viruses through deubiquitinating MITA. PLoS Pathog 16(1): e32767. doi:10.1371/journal.ppat.1008178
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.ppat.1008178
Souhrn
Mediator of IRF3 activation (MITA, also known as stimulator of interferon genes, STING) senses the second messenger cyclic GMP-AMP (cGAMP) which is synthesized upon DNA virus infection and activates innate antiviral immune response. It has been demonstrated that the activity of MITA is delicately regulated by various post-translational modifications including polyubiquitination. In this study, we identified the deubiquitinating enzyme USP44 as a positive regulator of MITA. USP44 is recruited to MITA following DNA virus infection and removes K48-linked polyubiquitin moieties from MITA at K236, therefore prevents MITA from proteasome mediated degradation. USP44-deficiency results in acceleration of HSV-1-induced degradation of MITA and reduced induction of type I interferons (IFNs) and proinflammatory cytokines. Consistently, Usp44-/- mice are more susceptible to HSV-1 infection as indicated by higher tissue viral titers, greater tissue damage and lower survival rate. These findings suggest that USP44 plays a specific and critical role in the regulation of innate immune response against DNA viruses.
Klíčová slova:
DNA transcription – DNA viruses – Enzyme regulation – Immune response – Immunoblotting – Interferons – Plasmid construction – Vector-borne diseases
Zdroje
1. Tan X, Sun L, Chen J, Chen ZJ. Detection of Microbial Infections Through Innate Immune Sensing of Nucleic Acids. Annual Review of Microbiology. 2018;72(1):447–78. doi: 10.1146/annurev-micro-102215-095605 30200854.
2. Medzhitov R. Recognition of microorganisms and activation of the immune response. Nature. 2007;449(7164):819–26. Epub 2007/10/19. doi: 10.1038/nature06246 17943118.
3. Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell. 2010;140(6):805–20. Epub 2010/03/23. doi: 10.1016/j.cell.2010.01.022 20303872.
4. Janeway CA Jr., Medzhitov R. Innate immune recognition. Annu Rev Immunol. 2002;20:197–216. Epub 2002/02/28. doi: 10.1146/annurev.immunol.20.083001.084359 11861602.
5. Akira S, Takeda K. Toll-like receptor signalling. Nature Reviews Immunology. 2004;4(7):499–511. doi: 10.1038/nri1391 15229469
6. Nakhaei P, Genin P, Civas A, Hiscott J. RIG-I-like receptors: sensing and responding to RNA virus infection. Semin Immunol. 2009;21(4):215–22. Epub 2009/06/23. doi: 10.1016/j.smim.2009.05.001 19539500.
7. Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, Matsui K, et al. Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature. 2006;441(7089):101–5. doi: 10.1038/nature04734 16625202
8. Lund J, Sato A, Akira S, Medzhitov R, Iwasaki A. Toll-like receptor 9-mediated recognition of Herpes simplex virus-2 by plasmacytoid dendritic cells. J Exp Med. 2003;198(3):513–20. Epub 2003/08/06. doi: 10.1084/jem.20030162 12900525; PubMed Central PMCID: PMC2194085.
9. Takaoka A, Wang Z, Choi MK, Yanai H, Negishi H, Ban T, et al. DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response. Nature. 2007;448(7152):501–5. Epub 2007/07/10. doi: 10.1038/nature06013 17618271.
10. Chiu YH, Macmillan JB, Chen ZJ. RNA polymerase III detects cytosolic DNA and induces type I interferons through the RIG-I pathway. Cell. 2009;138(3):576–91. Epub 2009/07/28. doi: 10.1016/j.cell.2009.06.015 19631370; PubMed Central PMCID: PMC2747301.
11. Unterholzner L, Keating SE, Baran M, Horan KA, Jensen SB, Sharma S, et al. IFI16 is an innate immune sensor for intracellular DNA. Nat Immunol. 2010;11(11):997–1004. Epub 2010/10/05. doi: 10.1038/ni.1932 20890285; PubMed Central PMCID: PMC3142795.
12. Zhang Z, Yuan B, Bao M, Lu N, Kim T, Liu YJ. The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells. Nat Immunol. 2011;12(10):959–65. Epub 2011/09/06. doi: 10.1038/ni.2091 21892174; PubMed Central PMCID: PMC3671854.
13. Li Y, Chen R, Zhou Q, Xu Z, Li C, Wang S, et al. LSm14A is a processing body-associated sensor of viral nucleic acids that initiates cellular antiviral response in the early phase of viral infection. Proceedings of the National Academy of Sciences. 2012;109(29):11770–5. doi: 10.1073/pnas.1203405109 22745163
14. Unterholzner L. The interferon response to intracellular DNA: why so many receptors? Immunobiology. 2013;218(11):1312–21. Epub 2013/08/22. doi: 10.1016/j.imbio.2013.07.007 23962476.
15. Sun L, Wu J, Du F, Chen X, Chen ZJ. Cyclic GMP-AMP Synthase Is a Cytosolic DNA Sensor That Activates the Type I Interferon Pathway. Science. 2013;339(6121):786–91. doi: 10.1126/science.1232458 23258413
16. Wu J, Sun L, Chen X, Du F, Shi H, Chen C, et al. Cyclic GMP-AMP Is an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA. Science. 2013;339(6121):826–30. doi: 10.1126/science.1229963 23258412
17. Civril F, Deimling T, de Oliveira Mann CC, Ablasser A, Moldt M, Witte G, et al. Structural mechanism of cytosolic DNA sensing by cGAS. Nature. 2013;498(7454):332–7. Epub 2013/06/01. doi: 10.1038/nature12305 23722159; PubMed Central PMCID: PMC3768140.
18. Zhong B, Yang Y, Li S, Wang YY, Li Y, Diao F, et al. The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation. Immunity. 2008;29(4):538–50. Epub 2008/09/27. doi: 10.1016/j.immuni.2008.09.003 18818105.
19. Ishikawa H, Barber GN. STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling. Nature. 2008;455(7213):674–8. doi: 10.1038/nature07317 18724357
20. Sun W, Li Y, Chen L, Chen H, You F, Zhou X, et al. ERIS, an endoplasmic reticulum IFN stimulator, activates innate immune signaling through dimerization. Proc Natl Acad Sci U S A. 2009;106(21):8653–8. Epub 2009/05/13. doi: 10.1073/pnas.0900850106 19433799; PubMed Central PMCID: PMC2689030.
21. Jin L, Waterman PM, Jonscher KR, Short CM, Reisdorph NA, Cambier JC. MPYS, a novel membrane tetraspanner, is associated with major histocompatibility complex class II and mediates transduction of apoptotic signals. Mol Cell Biol. 2008;28(16):5014–26. Epub 2008/06/19. doi: 10.1128/MCB.00640-08 18559423; PubMed Central PMCID: PMC2519703.
22. Barber GN. STING-dependent signaling. Nature Immunology. 2011;12:929. doi: 10.1038/ni.2118 21934672
23. Zhang X, Shi H, Wu J, Zhang X, Sun L, Chen C, et al. Cyclic GMP-AMP containing mixed phosphodiester linkages is an endogenous high-affinity ligand for STING. Mol Cell. 2013;51(2):226–35. Epub 2013/06/12. doi: 10.1016/j.molcel.2013.05.022 23747010; PubMed Central PMCID: PMC3808999.
24. Ishikawa H, Ma Z, Barber GN. STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature. 2009;461(7265):788–92. Epub 2009/09/25. doi: 10.1038/nature08476 19776740; PubMed Central PMCID: PMC4664154.
25. Dobbs N, Burnaevskiy N, Chen D, Gonugunta VK, Alto NM, Yan N. STING Activation by Translocation from the ER Is Associated with Infection and Autoinflammatory Disease. Cell Host Microbe. 2015;18(2):157–68. Epub 2015/08/04. doi: 10.1016/j.chom.2015.07.001 26235147; PubMed Central PMCID: PMC4537353.
26. Liu S, Cai X, Wu J, Cong Q, Chen X, Li T, et al. Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation. Science. 2015;347(6227):aaa2630–aaa. doi: 10.1126/science.aaa2630 25636800
27. Tanaka Y, Chen ZJ. STING Specifies IRF3 Phosphorylation by TBK1 in the Cytosolic DNA Signaling Pathway. Science Signaling. 2012;5(214):ra20–ra. doi: 10.1126/scisignal.2002521 22394562
28. Hu M-M, Shu H-B. Cytoplasmic Mechanisms of Recognition and Defense of Microbial Nucleic Acids. Annual Review of Cell and Developmental Biology. 2018;34(1):357–79. doi: 10.1146/annurev-cellbio-100617-062903 30095291.
29. Hu MM, Yang Q, Xie XQ, Liao CY, Lin H, Liu TT, et al. Sumoylation Promotes the Stability of the DNA Sensor cGAS and the Adaptor STING to Regulate the Kinetics of Response to DNA Virus. Immunity. 2016;45(3):555–69. Epub 2016/09/18. doi: 10.1016/j.immuni.2016.08.014 27637147.
30. Tsuchida T, Zou J, Saitoh T, Kumar H, Abe T, Matsuura Y, et al. The ubiquitin ligase TRIM56 regulates innate immune responses to intracellular double-stranded DNA. Immunity. 2010;33(5):765–76. Epub 2010/11/16. doi: 10.1016/j.immuni.2010.10.013 21074459.
31. Zhang J, Hu M-M, Wang Y-Y, Shu H-B. TRIM32 Protein Modulates Type I Interferon Induction and Cellular Antiviral Response by Targeting MITA/STING Protein for K63-linked Ubiquitination. Journal of Biological Chemistry. 2012;287(34):28646–55. doi: 10.1074/jbc.M112.362608 22745133
32. Wang Q, Liu X, Cui Y, Tang Y, Chen W, Li S, et al. The E3 ubiquitin ligase AMFR and INSIG1 bridge the activation of TBK1 kinase by modifying the adaptor STING. Immunity. 2014;41(6):919–33. Epub 2014/12/20. doi: 10.1016/j.immuni.2014.11.011 25526307.
33. Zhong B, Zhang L, Lei C, Li Y, Mao AP, Yang Y, et al. The ubiquitin ligase RNF5 regulates antiviral responses by mediating degradation of the adaptor protein MITA. Immunity. 2009;30(3):397–407. Epub 2009/03/17. doi: 10.1016/j.immuni.2009.01.008 19285439.
34. Qin Y, Zhou MT, Hu MM, Hu YH, Zhang J, Guo L, et al. RNF26 temporally regulates virus-triggered type I interferon induction by two distinct mechanisms. PLoS Pathog. 2014;10(9):e1004358. Epub 2014/09/26. doi: 10.1371/journal.ppat.1004358 25254379; PubMed Central PMCID: PMC4177927.
35. Chen M, Meng Q, Qin Y, Liang P, Tan P, He L, et al. TRIM14 Inhibits cGAS Degradation Mediated by Selective Autophagy Receptor p62 to Promote Innate Immune Responses. Mol Cell. 2016;64(1):105–19. Epub 2016/09/27. doi: 10.1016/j.molcel.2016.08.025 27666593.
36. Sun H, Zhang Q, Jing YY, Zhang M, Wang HY, Cai Z, et al. USP13 negatively regulates antiviral responses by deubiquitinating STING. Nat Commun. 2017;8:15534. Epub 2017/05/24. doi: 10.1038/ncomms15534 28534493; PubMed Central PMCID: PMC5457515.
37. Ye L, Zhang Q, Liuyu T, Xu Z, Zhang MX, Luo MH, et al. USP49 negatively regulates cellular antiviral responses via deconjugating K63-linked ubiquitination of MITA. PLoS Pathog. 2019;15(4):e1007680. Epub 2019/04/04. doi: 10.1371/journal.ppat.1007680 30943264; PubMed Central PMCID: PMC6464240.
38. Komander D, Clague MJ, Urbe S. Breaking the chains: structure and function of the deubiquitinases. Nat Rev Mol Cell Biol. 2009;10(8):550–63. Epub 2009/07/25. doi: 10.1038/nrm2731 19626045.
39. Stegmeier F, Rape M, Draviam VM, Nalepa G, Sowa ME, Ang XL, et al. Anaphase initiation is regulated by antagonistic ubiquitination and deubiquitination activities. Nature. 2007;446(7138):876–81. Epub 2007/04/20. doi: 10.1038/nature05694 17443180.
40. Zhang Y, van Deursen J, Galardy PJ. Overexpression of ubiquitin specific protease 44 (USP44) induces chromosomal instability and is frequently observed in human T-cell leukemia. PLoS One. 2011;6(8):e23389. Epub 2011/08/20. doi: 10.1371/journal.pone.0023389 PubMed Central PMCID: PMC3154946. 21853124
41. Fuchs G, Shema E, Vesterman R, Kotler E, Wolchinsky Z, Wilder S, et al. RNF20 and USP44 regulate stem cell differentiation by modulating H2B monoubiquitylation. Mol Cell. 2012;46(5):662–73. Epub 2012/06/12. doi: 10.1016/j.molcel.2012.05.023 22681888; PubMed Central PMCID: PMC3374598.
42. Zhang Y, Foreman O, Wigle DA, Kosari F, Vasmatzis G, Salisbury JL, et al. USP44 regulates centrosome positioning to prevent aneuploidy and suppress tumorigenesis. J Clin Invest. 2012;122(12):4362–74. Epub 2012/11/29. doi: 10.1172/JCI63084 23187126; PubMed Central PMCID: PMC3533537.
43. Mosbech A, Lukas C, Bekker-Jensen S, Mailand N. The Deubiquitylating Enzyme USP44 Counteracts the DNA Double-strand Break Response Mediated by the RNF8 and RNF168 Ubiquitin Ligases. Journal of Biological Chemistry. 2013;288(23):16579–87. doi: 10.1074/jbc.M113.459917 23615962
44. Lin YH, Forster M, Liang Y, Yu M, Wang H, Robert F, et al. USP44 is dispensable for normal hematopoietic stem cell function, lymphocyte development, and B-cell-mediated immune response in a mouse model. Experimental Hematology. 2019. doi: 10.1016/j.exphem.2019.01.001 30639577
45. Wang Y, Lian Q, Yang B, Yan S, Zhou H, He L, et al. TRIM30alpha Is a Negative-Feedback Regulator of the Intracellular DNA and DNA Virus-Triggered Response by Targeting STING. PLoS Pathog. 2015;11(6):e1005012. Epub 2015/06/27. doi: 10.1371/journal.ppat.1005012 26114947; PubMed Central PMCID: PMC4482643.
46. Li Q, Lin L, Tong Y, Liu Y, Mou J, Wang X, et al. TRIM29 negatively controls antiviral immune response through targeting STING for degradation. Cell Discov. 2018;4:13. Epub 2018/03/28. doi: 10.1038/s41421-018-0010-9 29581886; PubMed Central PMCID: PMC5859251.
47. Xing J, Zhang A, Zhang H, Wang J, Li XC, Zeng M-S, et al. TRIM29 promotes DNA virus infections by inhibiting innate immune response. Nature Communications. 2017;8(1). doi: 10.1038/s41467-017-00101-w 29038422
48. Zhang MX, Cai Z, Zhang M, Wang XM, Wang Y, Zhao F, et al. USP20 Promotes Cellular Antiviral Responses via Deconjugating K48-Linked Ubiquitination of MITA. J Immunol. 2019;202(8):2397–406. Epub 2019/03/01. doi: 10.4049/jimmunol.1801447 30814308.
49. Zhang L, Wei N, Cui Y, Hong Z, Liu X, Wang Q, et al. The deubiquitinase CYLD is a specific checkpoint of the STING antiviral signaling pathway. PLOS Pathogens. 2018;14(11):e1007435. doi: 10.1371/journal.ppat.1007435 30388174
50. Zhang M, Zhang M-X, Zhang Q, Zhu G-F, Yuan L, Zhang D-E, et al. USP18 recruits USP20 to promote innate antiviral response through deubiquitinating STING/MITA. Cell Research. 2016;26(12):1302–19. doi: 10.1038/cr.2016.125 27801882
51. Konno H, Konno K, Barber GN. Cyclic dinucleotides trigger ULK1 (ATG1) phosphorylation of STING to prevent sustained innate immune signaling. Cell. 2013;155(3):688–98. Epub 2013/10/15. doi: 10.1016/j.cell.2013.09.049 24119841; PubMed Central PMCID: PMC3881181.
52. Kim JH, Seo D, Kim SJ, Choi DW, Park JS, Ha J, et al. The deubiquitinating enzyme USP20 stabilizes ULK1 and promotes autophagy initiation. EMBO Rep. 2018;19(4). Epub 2018/03/01. doi: 10.15252/embr.201744378 29487085; PubMed Central PMCID: PMC5891421.
53. Kovalenko A, Chable-Bessia C, Cantarella G, Israël A, Wallach D, Courtois G. The tumour suppressor CYLD negatively regulates NF-κB signalling by deubiquitination. Nature. 2003;424(6950):801–5. doi: 10.1038/nature01802 12917691
54. Trompouki E, Hatzivassiliou E, Tsichritzis T, Farmer H, Ashworth A, Mosialos G. CYLD is a deubiquitinating enzyme that negatively regulates NF-κB activation by TNFR family members. Nature. 2003;424(6950):793–6. doi: 10.1038/nature01803 12917689
55. Zhang M, Wu X, Lee AJ, Jin W, Chang M, Wright A, et al. Regulation of IkappaB kinase-related kinases and antiviral responses by tumor suppressor CYLD. J Biol Chem. 2008;283(27):18621–6. Epub 2008/05/10. doi: 10.1074/jbc.M801451200 18467330; PubMed Central PMCID: PMC2441564.
56. Friedman CS, O'Donnell MA, Legarda-Addison D, Ng A, Cardenas WB, Yount JS, et al. The tumour suppressor CYLD is a negative regulator of RIG-I-mediated antiviral response. EMBO Rep. 2008;9(9):930–6. Epub 2008/07/19. doi: 10.1038/embor.2008.136 18636086; PubMed Central PMCID: PMC2529351.
57. Holland AJ, Cleveland DW. The deubiquitinase USP44 is a tumor suppressor that protects against chromosome missegregation. J Clin Invest. 2012;122(12):4325–8. Epub 2012/11/29. doi: 10.1172/JCI66420 23187131; PubMed Central PMCID: PMC3533566.
58. Kondo T, Kobayashi J, Saitoh T, Maruyama K, Ishii KJ, Barber GN, et al. DNA damage sensor MRE11 recognizes cytosolic double-stranded DNA and induces type I interferon by regulating STING trafficking. Proc Natl Acad Sci U S A. 2013;110(8):2969–74. Epub 2013/02/08. doi: 10.1073/pnas.1222694110 23388631; PubMed Central PMCID: PMC3581880.
59. Li Y, Wu Y, Zheng X, Cong J, Liu Y, Li J, et al. Cytoplasm-Translocated Ku70/80 Complex Sensing of HBV DNA Induces Hepatitis-Associated Chemokine Secretion. Front Immunol. 2016;7:569. Epub 2016/12/21. doi: 10.3389/fimmu.2016.00569 27994596; PubMed Central PMCID: PMC5136554.
60. Lian H, Wei J, Zang R, Ye W, Yang Q, Zhang X-N, et al. ZCCHC3 is a co-sensor of cGAS for dsDNA recognition in innate immune response. Nature Communications. 2018;9(1). doi: 10.1038/s41467-018-05559-w 30135424
61. Luo WW, Li S, Li C, Lian H, Yang Q, Zhong B, et al. iRhom2 is essential for innate immunity to DNA viruses by mediating trafficking and stability of the adaptor STING. Nat Immunol. 2016;17(9):1057–66. Epub 2016/07/19. doi: 10.1038/ni.3510 27428826.
62. Wei J, Lian H, Guo W, Chen YD, Zhang XN, Zang R, et al. SNX8 modulates innate immune response to DNA virus by mediating trafficking and activation of MITA. PLoS Pathog. 2018;14(10):e1007336. Epub 2018/10/16. doi: 10.1371/journal.ppat.1007336 30321235; PubMed Central PMCID: PMC6188873.
63. Luo WW, Li S, Li C, Zheng ZQ, Cao P, Tong Z, et al. iRhom2 is essential for innate immunity to RNA virus by antagonizing ER- and mitochondria-associated degradation of VISA. PLoS Pathog. 2017;13(11):e1006693. Epub 2017/11/21. doi: 10.1371/journal.ppat.1006693 29155878; PubMed Central PMCID: PMC5722342.
64. Yang Q, Liu TT, Lin H, Zhang M, Wei J, Luo WW, et al. TRIM32-TAX1BP1-dependent selective autophagic degradation of TRIF negatively regulates TLR3/4-mediated innate immune responses. PLoS Pathog. 2017;13(9):e1006600. Epub 2017/09/13. doi: 10.1371/journal.ppat.1006600 28898289; PubMed Central PMCID: PMC5595311.
65. Fu YZ, Guo Y, Zou HM, Su S, Wang SY, Yang Q, et al. Human cytomegalovirus protein UL42 antagonizes cGAS/MITA-mediated innate antiviral response. PLoS Pathog. 2019;15(5):e1007691. Epub 2019/05/21. doi: 10.1371/journal.ppat.1007691 31107917.
66. Nie Y, Ran Y, Zhang H-Y, Huang Z-F, Pan Z-Y, Wang S-Y, et al. GPATCH3 negatively regulates RLR-mediated innate antiviral responses by disrupting the assembly of VISA signalosome. PLOS Pathogens. 2017;13(4):e1006328. doi: 10.1371/journal.ppat.1006328 28414768
67. Zhou Q, Lin H, Wang S, Wang S, Ran Y, Liu Y, et al. The ER-associated protein ZDHHC1 is a positive regulator of DNA virus-triggered, MITA/STING-dependent innate immune signaling. Cell Host Microbe. 2014;16(4):450–61. Epub 2014/10/10. doi: 10.1016/j.chom.2014.09.006 25299331.
68. Yang Y, Wang SY, Huang ZF, Zou HM, Yan BR, Luo WW, et al. The RNA-binding protein Mex3B is a coreceptor of Toll-like receptor 3 in innate antiviral response. Cell Res. 2016;26(3):288–303. Epub 2016/01/30. doi: 10.1038/cr.2016.16 26823206; PubMed Central PMCID: PMC4783467.
69. Zhang Y, Lei CQ, Hu YH, Xia T, Li M, Zhong B, et al. Kruppel-like factor 6 is a co-activator of NF-kappaB that mediates p65-dependent transcription of selected downstream genes. J Biol Chem. 2014;289(18):12876–85. Epub 2014/03/19. doi: 10.1074/jbc.M113.535831 24634218; PubMed Central PMCID: PMC4007475.
70. Hu MM, Liao CY, Yang Q, Xie XQ, Shu HB. Innate immunity to RNA virus is regulated by temporal and reversible sumoylation of RIG-I and MDA5. J Exp Med. 2017;214(4):973–89. Epub 2017/03/03. doi: 10.1084/jem.20161015 28250012; PubMed Central PMCID: PMC5379974.
71. Huang ZF, Zou HM, Liao BW, Zhang HY, Yang Y, Fu YZ, et al. Human Cytomegalovirus Protein UL31 Inhibits DNA Sensing of cGAS to Mediate Immune Evasion. Cell Host Microbe. 2018;24(1):69–80 e4. Epub 2018/06/26. doi: 10.1016/j.chom.2018.05.007 29937271.
72. Xu ZS, Zhang HX, Zhang YL, Liu TT, Ran Y, Chen LT, et al. PASD1 promotes STAT3 activity and tumor growth by inhibiting TC45-mediated dephosphorylation of STAT3 in the nucleus. J Mol Cell Biol. 2016;8(3):221–31. Epub 2016/02/20. doi: 10.1093/jmcb/mjw005 26892021.
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