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The ubiquitin ligase TRAF6 negatively regulates the JAK-STAT signaling pathway by binding to STAT3 and mediating its ubiquitination.

Wei J, Yuan Y, Jin C, Chen H, Leng L, He F, Wang J.

PLoS One. 2012;7(11):e49567. doi: 10.1371/journal.pone.0049567. Epub 2012 Nov 19.


Site-specific Lys-63-linked tumor necrosis factor receptor-associated factor 6 auto-ubiquitination is a critical determinant of I kappa B kinase activation.

Lamothe B, Besse A, Campos AD, Webster WK, Wu H, Darnay BG.

J Biol Chem. 2007 Feb 9;282(6):4102-12. Epub 2006 Nov 29.


The PP4R1 subunit of protein phosphatase PP4 targets TRAF2 and TRAF6 to mediate inhibition of NF-κB activation.

Hadweh P, Habelhah H, Kieff E, Mosialos G, Hatzivassiliou E.

Cell Signal. 2014 Dec;26(12):2730-7. doi: 10.1016/j.cellsig.2014.08.001. Epub 2014 Aug 16.


Mutational analysis of TRAF6 reveals a conserved functional role of the RING dimerization interface and a potentially necessary but insufficient role of RING-dependent TRAF6 polyubiquitination towards NF-κB activation.

Megas C, Hatzivassiliou EG, Yin Q, Marinopoulou E, Hadweh P, Vignali DA, Mosialos G.

Cell Signal. 2011 May;23(5):772-7. doi: 10.1016/j.cellsig.2010.12.004. Epub 2010 Dec 23.


Ubiquitin-specific peptidase USP22 negatively regulates the STAT signaling pathway by deubiquitinating SIRT1.

Ao N, Liu Y, Feng H, Bian X, Li Z, Gu B, Zhao X, Liu Y.

Cell Physiol Biochem. 2014;33(6):1863-75. doi: 10.1159/000362964. Epub 2014 Jun 23.


Phosphoinositide-dependent kinase-1 inhibits TRAF6 ubiquitination by interrupting the formation of TAK1-TAB2 complex in TLR4 signaling.

Moon G, Kim J, Min Y, Wi SM, Shim JH, Chun E, Lee KY.

Cell Signal. 2015 Dec;27(12):2524-33. doi: 10.1016/j.cellsig.2015.09.018. Epub 2015 Sep 30.


Hsp70 inhibits lipopolysaccharide-induced NF-kappaB activation by interacting with TRAF6 and inhibiting its ubiquitination.

Chen H, Wu Y, Zhang Y, Jin L, Luo L, Xue B, Lu C, Zhang X, Yin Z.

FEBS Lett. 2006 May 29;580(13):3145-52. Epub 2006 May 2.


STAT3 restrains RANK- and TLR4-mediated signalling by suppressing expression of the E2 ubiquitin-conjugating enzyme Ubc13.

Zhang H, Hu H, Greeley N, Jin J, Matthews AJ, Ohashi E, Caetano MS, Li HS, Wu X, Mandal PK, McMurray JS, Moghaddam SJ, Sun SC, Watowich SS.

Nat Commun. 2014 Dec 15;5:5798. doi: 10.1038/ncomms6798.


Tumor Necrosis Factor Receptor-Associated Factor 6 (TRAF6) Mediates Ubiquitination-Dependent STAT3 Activation upon Salmonella enterica Serovar Typhimurium Infection.

Ruan HH, Zhang Z, Wang SY, Nickels LM, Tian L, Qiao JJ, Zhu J.

Infect Immun. 2017 Jul 19;85(8). pii: e00081-17. doi: 10.1128/IAI.00081-17. Print 2017 Aug.


Ubiquitin-specific protease 4 (USP4) targets TRAF2 and TRAF6 for deubiquitination and inhibits TNFα-induced cancer cell migration.

Xiao N, Li H, Luo J, Wang R, Chen H, Chen J, Wang P.

Biochem J. 2012 Feb 1;441(3):979-86. doi: 10.1042/BJ20111358.


Tumor necrosis factor (TNF) receptor-associated factor (TRAF)-interacting protein (TRIP) negatively regulates the TRAF2 ubiquitin-dependent pathway by suppressing the TRAF2-sphingosine 1-phosphate (S1P) interaction.

Park ES, Choi S, Shin B, Yu J, Yu J, Hwang JM, Yun H, Chung YH, Choi JS, Choi Y, Rho J.

J Biol Chem. 2015 Apr 10;290(15):9660-73. doi: 10.1074/jbc.M114.609685. Epub 2015 Feb 25.


JAK2 inhibitor blocks the inflammation and growth of esophageal squamous cell carcinoma in vitro through the JAK/STAT3 pathway.

Fang J, Chu L, Li C, Chen Y, Hu F, Zhang X, Zhao H, Liu Z, Xu Q.

Oncol Rep. 2015 Jan;33(1):494-502. doi: 10.3892/or.2014.3609. Epub 2014 Nov 14.


The coiled-coil domain of TRAF6 is essential for its auto-ubiquitination.

Yang K, Zhu J, Sun S, Tang Y, Zhang B, Diao L, Wang C.

Biochem Biophys Res Commun. 2004 Nov 5;324(1):432-9.


Negative regulation of the retinoic acid-inducible gene I-induced antiviral state by the ubiquitin-editing protein A20.

Lin R, Yang L, Nakhaei P, Sun Q, Sharif-Askari E, Julkunen I, Hiscott J.

J Biol Chem. 2006 Jan 27;281(4):2095-103. Epub 2005 Nov 23.


Schizandrin A Inhibits Microglia-Mediated Neuroninflammation through Inhibiting TRAF6-NF-κB and Jak2-Stat3 Signaling Pathways.

Song F, Zeng K, Liao L, Yu Q, Tu P, Wang X.

PLoS One. 2016 Feb 26;11(2):e0149991. doi: 10.1371/journal.pone.0149991. eCollection 2016.


Ubiquitin-associated domain-containing ubiquitin regulatory X (UBX) protein UBXN1 is a negative regulator of nuclear factor κB (NF-κB) signaling.

Wang YB, Tan B, Mu R, Chang Y, Wu M, Tu HQ, Zhang YC, Guo SS, Qin XH, Li T, Li WH, Li AL, Zhang XM, Li HY.

J Biol Chem. 2015 Apr 17;290(16):10395-405. doi: 10.1074/jbc.M114.631689. Epub 2015 Feb 13.


JAK/STAT pathway plays a critical role in the proinflammatory gene expression and apoptosis of RAW264.7 cells induced by trichothecenes as DON and T-2 toxin.

Wang X, Liu Q, Ihsan A, Huang L, Dai M, Hao H, Cheng G, Liu Z, Wang Y, Yuan Z.

Toxicol Sci. 2012 Jun;127(2):412-24. doi: 10.1093/toxsci/kfs106. Epub 2012 Mar 27.


The ubiquitin-editing enzyme A20 requires RNF11 to downregulate NF-kappaB signalling.

Shembade N, Parvatiyar K, Harhaj NS, Harhaj EW.

EMBO J. 2009 Mar 4;28(5):513-22. doi: 10.1038/emboj.2008.285. Epub 2009 Jan 8.


Stimulation of the JAK/STAT pathway by LIF and OSM in the human granulosa cell line COV434.

Pastuschek J, Poetzsch J, Morales-Prieto DM, Schleußner E, Markert UR, Georgiev G.

J Reprod Immunol. 2015 Apr;108:48-55. doi: 10.1016/j.jri.2015.03.002. Epub 2015 Mar 16.


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