title: Induction of TRIM22 by IFN-γ Involves JAK and PC-PLC/PKC, but Not MAPKs and pI3K/Akt/mTOR Pathways.
abstract: Tripartite motif (TRIM) 22 plays an important role in interferons (IFNs)-mediated antiviral activity. We previously demonstrated that interferon regulatory factor-1 (IRF-1) played a central role in IFN-γ-induced TRIM22 expression via binding to a special cis-element named 5' extended IFN-stimulating response element (5'eISRE). In this study, we sought to identify the signaling pathways involved in TRIM22 induction by IFN-γ. By using various pharmacological inhibitors, it was found that the activity of tyrosine kinase and phosphatidylcholine-phospholipase C (PC-PLC), but not phosphatidylinositol-phospholipase C (PI-PLC) and phospholipase D (PLD), was required for IFN-γ-induced TRIM22 expression in HepG2 cells. Tyrosine kinase Janus kinase (JAK), not SRC and PYK2, played an indispensable role in TRIM22 induction. Inhibition of protein kinase C (PKC) activity also significantly attenuated IFN-γ induction of TRIM22. Although treatment with IFN-γ resulted in the stimulation of mitogen-activated protein kinases (MAPKs) (p38, ERK, and JNK) and pI3K/Akt/mTOR pathways in HepG2 cells, the inhibition of their activity did not affect IFN-γ-stimulated TRIM22 expression. Further studies showed that overexpression of JAK1 and PKCα activated TRIM22 promoter activity in a 5'eISRE-dependent manner, and inhibition of not only JAK but also PC-PLC/PKC pathways significantly attenuated IFN-γ-induced IRF-1 expression in HepG2 cells. Taken together, these data indicated that IFN-γ induced TRIM22 expression via activation of JAK and PC-PLC/PKC signaling pathways, which involved the cis-element 5'eISRE and the transactivator IRF-1.
authors: 1 Department of Immunology, Institute for Immunobiology, Shanghai Medical College of Fudan University , Shanghai, P.R. China .
authors: Bo
authors: B
authors: Gao
authors: Wei
authors: W
authors: Xu
authors: Yaxin
authors: Y
authors: Wang
authors: Linmao
authors: L
authors: Zhong
authors: Sidong
authors: S
authors: Xiong
mesh_terms: D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051418:Focal Adhesion Kinase 2 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D053612:Janus Kinases / Q000378:metabolism*; D015778:Minor Histocompatibility Antigens; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases; D014158:Transcription, Genetic / Q000187:drug effects; D000070584:Tripartite Motif Proteins; D010738:Type C Phospholipases / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D051418:Focal Adhesion Kinase 2; D007371:Interferon-gamma; D053612:Janus Kinases; D015778:Minor Histocompatibility Antigens; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D047428:Protein Kinase Inhibitors; D012097:Repressor Proteins; D058570:TOR Serine-Threonine Kinases; D000070584:Tripartite Motif Proteins; D010738:Type C Phospholipases; D019061:src-Family Kinases; C094314:TRIM22 protein, human; C105598:phosphatidylcholine-specific phospholipase C
references: J Biol Chem. 2004 Oct 1;279(40):41679-85
references: 15284232
references: J Biol Chem. 1995 Jun 23;270(25):14891-8
references: 7797467
references: J Gen Virol. 2009 Mar;90(Pt 3):536-545
references: 19218198
references: J Virol. 2011 May;85(10):5183-96
references: 21345949
references: Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15669-74
references: 12441396
references: Nat Rev Immunol. 2005 May;5(5):375-86
references: 15864272
references: Cell. 2006 Jan 13;124(1):207-19
references: 16413492
references: Nat Rev Cancer. 2011 Oct 07;11(11):792-804
references: 21979307
references: Atherosclerosis. 2004 Oct;176(2):279-87
references: 15380450
references: J Immunol. 2003 Jul 1;171(1):267-73
references: 12817007
references: FASEB J. 1995 Apr;9(7):484-96
references: 7737456
references: Exp Cell Res. 2006 May 1;312(8):1229-39
references: 16427044
references: J Biol Chem. 2007 Jan 19;282(3):1757-68
references: 17114181
references: Cell Signal. 2006 Apr;18(4):508-18
references: 16157472
references: J Immunol. 2003 Oct 15;171(8):4187-94
references: 14530341
references: J Biol Chem. 2007 May 18;282(20):15208-16
references: 17395590
references: Biochim Biophys Acta. 2009 Sep;1791(9):956-61
references: 19250975
references: Chem Rev. 2001 Aug;101(8):2353-64
references: 11749377
references: J Immunol. 2009 Jul 15;183(2):856-64
references: 19542364
references: J Biol Chem. 2002 Mar 1;277(9):7118-26
references: 11751911
references: PLoS Pathog. 2008 Feb 29;4(2):e1000007
references: 18389079
references: Proc Natl Acad Sci U S A. 2004 Apr 27;101(17):6669-74
references: 15100412
references: Curr Top Microbiol Immunol. 2007;316:119-54
references: 17969446
references: J Med Virol. 2007 Nov;79(11):1783-91
references: 17854033
references: J Interferon Cytokine Res. 2000 Nov;20(11):955-61
references: 11096452
references: J Virol. 2000 May;74(9):4174-82
references: 10756030
references: J Biol Chem. 2009 Feb 6;284(6):3700-8
references: 19075017
references: J Interferon Cytokine Res. 2005 Dec;25(12):780-7
references: 16375606
references: Biochem Biophys Res Commun. 2011 Jul 29;411(2):259-64
references: 21723260
references: Biochem Biophys Res Commun. 1995 Dec 14;217(2):546-53
references: 7503734
references: Biochem Biophys Res Commun. 2011 Jul 8;410(3):549-54
references: 21683060
references: Leuk Res. 2007 Jul;31(7):995-1001
references: 17257675
references: J Interferon Cytokine Res. 2005 Dec;25(12):749-56
references: 16375603
references: Virology. 2006 Dec 5-20;356(1-2):79-94
references: 16926043
references: Nat Rev Immunol. 2011 Aug 25;11(9):617-25
references: 21866173
references: J Immunol. 2010 Aug 15;185(4):2314-23
references: 20631312
references: PLoS One. 2009;4(3):e4894
references: 19290053
references: Cytokine Growth Factor Rev. 2007 Oct-Dec;18(5-6):419-23
references: 17683974
references: J Virol. 2011 Jan;85(1):208-16
references: 20980524
references: Mol Biol Int. 2012;2012:153415
references: 22649727
references: Nat Rev Microbiol. 2005 Oct;3(10):799-808
references: 16175175
references: EMBO J. 1999 May 4;18(9):2480-8
references: 10228162
references: Oncogene. 2004 May 20;23(23):4050-9
references: 15064739
references: Biochem Biophys Res Commun. 1994 Mar 15;199(2):461-6
references: 7510953
references: J Immunol. 2010 Sep 1;185(5):3041-8
references: 20675591
references: EMBO J. 2001 May 1;20(9):2140-51
references: 11331580
references: EMBO J. 1994 Jan 1;13(1):158-67
references: 8306959
references: Hepatology. 2009 Aug;50(2):424-33
references: 19585648
references: Nat Rev Immunol. 2008 Nov;8(11):849-60
references: 18836477
references: J Biol Chem. 2004 Oct 29;279(44):46335-42
references: 15322136