Adipocyte Biology Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
Department of Biological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA.
J Mol Endocrinol. 2018 Oct 15;61(4):195-205. doi: 10.1530/JME-18-0154.
STAT5A (signal transducer and activator of transcription 5A) is a transcription factor that plays a role in adipocyte development and function. In this study, we report DBC1 (deleted in breast cancer 1; also known as CCAR2) as a novel STAT5A-interacting protein. DBC1 has been primarily studied in tumor cells, but there is evidence that loss of this protein may promote metabolic health in mice. Currently, the functions of DBC1 in mature adipocytes are largely unknown. Using immunoprecipitation and immunoblotting techniques, we confirmed that there is an association between endogenous STAT5A and DBC1 proteins under physiological conditions in the adipocyte nucleus that is not dependent upon STAT5A tyrosine phosphorylation. We used siRNA to knockdown DBC1 in 3T3-L1 adipocytes to determine the impact on STAT5A activity, adipocyte gene expression, and TNFα (tumor necrosis factor α)-regulated lipolysis. The loss of DBC1 did not affect the expression of several STAT5A target genes including , , , , and However, we did observe decreased levels of TNFα-induced glycerol and free fatty acids released from adipocytes with reduced DBC1 expression. In addition, DBC1-knockdown adipocytes had increased expression. In summary, DBC1 can associate with STAT5A in adipocyte nucleus, but it does not appear to impact regulation of STAT5A target genes. Loss of adipocyte DBC1 modestly increases gene expression and reduces TNFα-induced lipolysis. These observations are consistent with observations that show loss of DBC1 promotes metabolic health in mice.
STAT5A（信号转导和转录激活因子 5A）是一种转录因子，在脂肪细胞发育和功能中发挥作用。在这项研究中，我们报告 DBC1（乳腺癌 1 缺失；也称为 CCAR2）作为一种新型 STAT5A 相互作用蛋白。DBC1 主要在肿瘤细胞中进行研究，但有证据表明该蛋白的缺失可能会促进小鼠的代谢健康。目前，DBC1 在成熟脂肪细胞中的功能在很大程度上尚不清楚。使用免疫沉淀和免疫印迹技术，我们在脂肪细胞核中证实了内源性 STAT5A 和 DBC1 蛋白在生理条件下存在关联，而这种关联不依赖于 STAT5A 酪氨酸磷酸化。我们使用 siRNA 敲低 3T3-L1 脂肪细胞中的 DBC1，以确定其对 STAT5A 活性、脂肪细胞基因表达和 TNFα（肿瘤坏死因子 α）调节的脂肪分解的影响。DBC1 的缺失并不影响包括 、 、 、 和 在内的几个 STAT5A 靶基因的表达。然而，我们确实观察到 DBC1 表达降低会导致 TNFα 诱导的甘油和游离脂肪酸从脂肪细胞中释放减少。此外，DBC1 敲低的脂肪细胞中 表达增加。总之，DBC1 可以在脂肪细胞核中与 STAT5A 结合，但似乎不会影响 STAT5A 靶基因的调节。脂肪细胞 DBC1 的缺失适度增加 基因表达并减少 TNFα 诱导的脂肪分解。这些观察结果与表明 DBC1 缺失促进小鼠代谢健康的 观察结果一致。
