KCTD1: A novel modulator of adipogenesis through the interaction with the transcription factor AP2α
KCTD1: A novel modulator of adipogenesis through the interaction with the transcription factor AP2α
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DOI：
10.1016/j.bbalip.2019.08.010
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发表时间：
2019-12-01
影响因子：
4.8
通讯作者：
Pedone, Emilia
中科院分区：
文献类型：
--
作者：
Pirone, Luciano;Smaldone, Giovanni;Pedone, Emilia
脂肪生成在调节能量平衡、组织动态平衡和疾病发病机制中具有重要作用。3T3-L1前脂肪细胞已被广泛用作研究脂肪细胞分化的体外模型。我们的研究表明，KCTD1是一个含有四聚结构域蛋白的钾通道成员，它在脂肪形成中起着积极的作用。特别是，我们发现KCTD1的表达在3T3-L1细胞在成脂诱导过程中增加。用Kctd1特异性siRNA处理3T3-L1前脂肪细胞可抑制分化，表现为特异性成脂标记物C/EBPA、PPARγ2、GLUT4和脂联素的表达减少。此外，我们还表明，该蛋白在体外和细胞内都与转录因子AP2α相互作用，AP2α是一种已知的脂肪生成抑制因子。有趣的是，我们的数据表明，KCTD1通过与AP2αa相互作用并将其从细胞核中移除来促进脂肪生成。总而言之，这些发现揭示了KCTD1的新作用，并为旨在调节脂肪形成的新策略铺平了道路。
Adipogenesis has an important role in regulating energy balance, tissue homeostasis and disease pathogenesis. 3T3-L1 preadipocytes have been widely used as an in vitro model for studying adipocyte differentiation. We here show that KCTD1, a member of the potassium channel containing tetramerization domain proteins, plays an active role in adipogenesis. In particular, we show KCTD1 expression 3T3-L1 cells increases upon adipogenesis induction. Treatment of 3T3-L1 preadipocytes with Kctd1-specific siRNA inhibited the differentiation, as indicated by reduction of expression of the specific adipogenic markers C/ebpa, Ppar gamma 2, Glut4, and Adiponectin. Moreover, we also show that the protein physically interacts with the transcription factor AP2 alpha, a known inhibitor of adipogenesis, both in vitro and in cells. Interestingly, our data indicate that KCTD1 promotes adipogenesis through the interaction with AP2 alpha a and by removing it from the nucleus. Collectively, these findings disclose a novel role for KCTD1 and pave the way for novel strategies aimed at modulating adipogenesis.