Functional Analysis of a Novel Obesity-associated E3 Ubiquitin Ligase WWP1

众所周知，肿瘤抑制因子p53转录调节几种E3泛素连接酶的表达，并且连接酶在转录后调节p53本身。我们发现p53靶向的E3泛素连接酶WWP 1的表达在肥胖小鼠的白色脂肪组织（WAT）中特异性上调。胰岛素给药降低了肥胖小鼠WAT中WWP 1蛋白的表达。此外，WWP 1的敲低抑制了3 T3-L1前脂肪细胞系中的脂肪细胞分化。我们的研究结果表明，WWP 1是一种新的肥胖WAT的标志蛋白，其表达受p53和胰岛素的调控。

It is well known that tumor suppressor p53 transcriptionally regulates the expression of several E3 ubiquitin ligases and the ligases post-translationally modulate p53 itself. We found that the expression of p53-targeted E3 ubiquitin ligase WWP1 was specifically up-regulated in white adipose tissue(WAT) of obese mice. An insulin administration reduced the expression of WWP1 protein in WAT in obese mice. Moreover, a knockdown for WWP1 suppressed adipocyte differentiation in 3T3-L1 preadipocyte cell line. Our findings suggest that WWP1 is a novel marker protein of obese WAT, and its expression is regulated by both p53 and insulin.