IDENTIFICATION OF PROTEINS THAT REGULATE THE SIN3A HISTONE DEACETYLASE COMPLEX

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 组蛋白翻译后修饰在基因调控、染色质包装和细胞分化中起着关键作用。组蛋白脱乙酰酶(HDACs)mSin3A复合体参与转录抑制，并含有多个参与生长控制的亚基，包括HDAC1和2，乳腺癌转移抑制蛋白1(BRMS1和BRMS1L1)，以及p33/ING1肿瘤抑制蛋白。然而，我们的初步数据表明，在不同的细胞类型和不同的生长条件下，mSin3A复合体的组成可能不同。分离和鉴定不同的Sin3A亚基对于阐明各种mSin3A复合体的作用是必不可少的。利用质谱学，我们的目标是识别相关蛋白质，并确定它们如何与其他亚基相互作用。这些数据将指导功能研究，以确定对细胞增殖、基因表达和基因组稳定性的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Histone post-translational modifications play a pivotal role in gene regulation, chromatin packaging and cellular differentiation. The histone deacetylase (HDACs) mSin3A complex is involved in transcriptional repression and contains multiple subunits that have been implicated in growth control, including HDAC 1 and 2, the Breast Suppressor of Metastasis 1 proteins (BRMS1 and BRMS1L1), and the p33/ING1 tumor suppressor proteins. However, our preliminary data suggest that mSin3A complex may be compositionally diverse in different cell types and under different growth conditions. Isolation and characterization of different Sin3A subunits is essential for elucidating the role of the various mSin3A complexes. Using mass spectroscopy, we aim to identify associated proteins, and determine how they interact with other subunits. These data will guide functional studies to determine effects on cell proliferation, gene expression and genomic stability.