Protein inhibitor of activated STAT 1 (PIAS1) is identified as the SUMO E3 ligase of CCAAT/enhancer-binding protein β (C/EBPβ) during adipogenesis.
It is well recognized that PIAS1, a SUMO (small ubiquitin-like modifier) E3 ligase, modulates such cellular processes as cell proliferation, DNA damage responses, and inflammation responses. Recent studies have shown that PIAS1 also plays a part in cell differentiation. However, the role of PIAS1 in adipocyte differentiation remains unknown. CCAAT/enhancer-binding protein β (C/EBPβ), a major regulator of adipogenesis, is a target of SUMOylation, but the E3 ligase responsible for the SUMOylation of C/EBPβ has not been identified. The present study showed that PIAS1 functions as a SUMO E3 ligase of C/EBPβ to regulate adipogenesis. PIAS1 expression was significantly and transiently induced on day 4 of 3T3-L1 adipocyte differentiation, when C/EBPβ began to decline. PIAS1 was found to interact with C/EBPβ through the SAP (scaffold attachment factor A/B/acinus/PIAS) domain and SUMOylate it, leading to increased ubiquitination and degradation of C/EBPβ. C/EBPβ became more stable when PIAS1 was silenced by RNA interference (RNAi). Moreover, adipogenesis was inhibited by overexpression of wild-type PIAS1 and promoted by knockdown of PIAS1. The mutational study indicated that the catalytic activity of SUMO E3 ligase was required for PIAS1 to restrain adipogenesis. Importantly, the inhibitory effect of PIAS1 overexpression on adipogenesis was rescued by overexpressed C/EBPβ. Thus, PIAS1 could play a dynamic role in adipogenesis by promoting the SUMOylation of C/EBPβ.
Key Laboratory of Molecular Medicine, Ministry of Education, and Department of Biochemistry and Molecular Biology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China.
Yang
Y
Liu
Ya-Dong
YD
Zhang
Liang
L
Guo
Hai-Yan
HY
Huang
Hao
H
Zhu
Jia-Xin
JX
Huang
Yuan
Y
Liu
Shui-Rong
SR
Zhou
Yong-Jun
YJ
Dang
Xi
X
Li
Qi-Qun
QQ
Tang
D041721:3T3-L1 Cells; D050156:Adipogenesis; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000737:chemistry / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D050828:Protein Inhibitors of Activated STAT / Q000235:genetics / Q000378:metabolism*; D055550:Protein Stability; D059748:Proteolysis; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D058207:Sumoylation; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination
D022782:CCAAT-Enhancer-Binding Protein-beta; D050828:Protein Inhibitors of Activated STAT; D025841:Small Ubiquitin-Related Modifier Proteins; D044767:Ubiquitin-Protein Ligases