| First Author | Liu Y | Year | 2013 |
| Journal | Mol Cell Biol | Volume | 33 |
| Issue | 22 | Pages | 4606-17 |
| PubMed ID | 24061474 | Mgi Jnum | J:219047 |
| Mgi Id | MGI:5619430 | Doi | 10.1128/MCB.00723-13 |
| Citation | Liu Y, et al. (2013) Protein inhibitor of activated STAT 1 (PIAS1) is identified as the SUMO E3 ligase of CCAAT/enhancer-binding protein beta (C/EBPbeta) during adipogenesis. Mol Cell Biol 33(22):4606-17 |
| abstractText | 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 beta (C/EBPbeta), a major regulator of adipogenesis, is a target of SUMOylation, but the E3 ligase responsible for the SUMOylation of C/EBPbeta has not been identified. The present study showed that PIAS1 functions as a SUMO E3 ligase of C/EBPbeta to regulate adipogenesis. PIAS1 expression was significantly and transiently induced on day 4 of 3T3-L1 adipocyte differentiation, when C/EBPbeta began to decline. PIAS1 was found to interact with C/EBPbeta through the SAP (scaffold attachment factor A/B/acinus/PIAS) domain and SUMOylate it, leading to increased ubiquitination and degradation of C/EBPbeta. C/EBPbeta 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/EBPbeta. Thus, PIAS1 could play a dynamic role in adipogenesis by promoting the SUMOylation of C/EBPbeta. |
