TRIM8 modulates STAT3 activity through negative regulation of PIAS3.
TRIM8 is a member of the protein family defined by the presence of a common domain structure composed of a tripartite motif: a RING-finger, one or two B-box domains and a coiled-coil motif. Here, we show that TRIM8 interacts with protein inhibitor of activated STAT3 (PIAS3), which inhibits IL-6-dependent activation of STAT3. Ectopic expression of TRIM8 cancels the negative effect of PIAS3 on STAT3, either by degradation of PIAS3 through the ubiquitin-proteasome pathway or exclusion of PIAS3 from the nucleus. Furthermore, expression of TRIM8 in NIH3T3 cells enhances Src-dependent tumorigenesis. These findings indicate that TRIM8 enhances the STAT3-dependent signal pathway by inhibiting the function of PIAS3.
Department of Biochemistry, Hokkaido University Graduate School of Medicine, N15, W7, Kita-ku, Sapporo, Hokkaido 060-8638, Japan.
Fumihiko
F
Okumura
Yui
Y
Matsunaga
Yuta
Y
Katayama
Keiichi I
KI
Nakayama
Shigetsugu
S
Hatakeyama
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D041681:NIH 3T3 Cells; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D050828:Protein Inhibitors of Activated STAT / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques; D054875:Ubiquitination; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism
D002352:Carrier Proteins; D015850:Interleukin-6; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; C484745:PIAS3 protein, human; D050828:Protein Inhibitors of Activated STAT; D050796:STAT3 Transcription Factor; C418604:TRIM8 protein, human; D019061:src-Family Kinases