The role of TACC3 in adipocyte differentiation
Transforming acidic coiled-coil (TACC) family is a group of proteins containing common C-terminal acidic coiled-coil domain, firstly found in cancer cells. TACC proteins were hypothesized to be involved in cellular growth and differentiation. TACC3, one of TACC family members, is highly expressed during embryonic development and adipocyte differentiation. Currently, the role of TACC3 in adipogenesis is still unknown. GSK3, a multifunction kinase also important for adipocyte development, has recently identified in our lab to negatively regulate TACC3 protein stability by phosphorylation in association with ubiquitin-dependent degradation pathway via SCFFbw2 E3 ligases. Here, we asked whether TACC3 is involved in the differentiation process of adipocytes and whether TACC3 stability is regulated by GSK3 in the process. We demonstrated that the level of TACC3 protein can be induced in early phase and declined during differentiation process of 3T3-L1 in late stage, which is essential for adipogenesis. TACC3 attenuated the levels of several master adipogenic transcription factors. Inhibition of GSK3 by LiCl resulted in an increase of TACC3 protein level, correlating with a suppression of lipid formation. In addition, depletion of TACC3 level by shRNA led to partially abolish the repressive effect of LiCl on adipogenesis. These results suggest that TACC3 plays a negatively regulatory role in adipocyte differentiation.
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