Chaubal Ashlesha, Todi Sokol V, Pile Lori A
From the Department of Biological Sciences, Wayne State University, Detroit, Michigan 48202 and.
the Department of Pharmacology, Wayne State University, Detroit, Michigan 48201.
J Biol Chem. 2016 May 27;291(22):11566-71. doi: 10.1074/jbc.C116.724799. Epub 2016 Apr 20.
SIN3 is a transcriptional corepressor that acts as a scaffold for a histone deacetylase (HDAC) complex. The SIN3 complex regulates various biological processes, including organ development, cell proliferation, and energy metabolism. Little is known, however, about the regulation of SIN3 itself. There are two major isoforms of Drosophila SIN3, 187 and 220, which are differentially expressed. Intrigued by the developmentally timed exchange of SIN3 isoforms, we examined whether SIN3 187 controls the fate of the 220 counterpart. Here, we show that in developing tissue, there is interplay between SIN3 isoforms: when SIN3 187 protein levels increase, SIN3 220 protein decreases concomitantly. SIN3 187 has a dual effect on SIN3 220. Expression of 187 leads to reduced 220 transcript, while also increasing the turnover of SIN3 220 protein by the proteasome. These data support the presence of a novel, inter-isoform-dependent mechanism that regulates the amount of SIN3 protein, and potentially the level of specific SIN3 complexes, during distinct developmental stages.
SIN3是一种转录共抑制因子，作为组蛋白去乙酰化酶（HDAC）复合物的支架发挥作用。SIN3复合物调节多种生物学过程，包括器官发育、细胞增殖和能量代谢。然而，关于SIN3自身的调节机制却知之甚少。果蝇SIN3有两种主要的异构体，即187和220，它们的表达存在差异。受SIN3异构体在发育过程中适时交换的启发，我们研究了SIN3 187是否控制其对应异构体220的命运。在此，我们表明在发育中的组织中，SIN3异构体之间存在相互作用：当SIN3 187蛋白水平升高时，SIN3 220蛋白会随之减少。SIN3 187对SIN3 220具有双重作用。187的表达导致220转录本减少，同时还会增加蛋白酶体对SIN3 220蛋白的降解。这些数据支持存在一种新的、异构体间依赖的机制，该机制在不同发育阶段调节SIN3蛋白的量，并可能调节特定SIN3复合物的水平。
