Department of Biochemistry and Molecular Biology, Center forCancer Epigenetics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Box 1000, Houston, Texas 77030, USA.
Mol Cell Biol. 2011 Aug;31(15):3126-35. doi: 10.1128/MCB.01350-10. Epub 2011 May 31.
Posttranslational modifications of histone proteins play important roles in the modulation of gene expression. The Saccharomyces cerevisiae (yeast) 2-MDa SAGA (Spt-Ada-Gcn5) complex, a well-studied multisubunit histone modifier, regulates gene expression through Gcn5-mediated histone acetylation and Ubp8-mediated histone deubiquitination. Using a proteomics approach, we determined that the SAGA complex also deubiquitinates nonhistone proteins, including Snf1, an AMP-activated kinase. Ubp8-mediated deubiquitination of Snf1 affects the stability and phosphorylation state of Snf1, thereby affecting Snf1 kinase activity. Others have reported that Gal83 is phosphorylated by Snf1, and we found that deletion of UBP8 causes decreased phosphorylation of Gal83, which is consistent with the effects of Ubp8 loss on Snf1 kinase functions. Overall, our data indicate that SAGA modulates the posttranslational modifications of Snf1 in order to fine-tune gene expression levels.
组蛋白蛋白的翻译后修饰在调节基因表达中起着重要作用。酿酒酵母（酵母）2-MDa SAGA（Spt-Ada-Gcn5）复合物是一种研究充分的多亚基组蛋白修饰物，通过 Gcn5 介导的组蛋白乙酰化和 Ubp8 介导的组蛋白去泛素化来调节基因表达。我们使用蛋白质组学方法确定，SAGA 复合物还可以去泛素化非组蛋白蛋白，包括 AMP 激活的激酶 Snf1。Ubp8 介导的 Snf1 去泛素化影响 Snf1 的稳定性和磷酸化状态，从而影响 Snf1 激酶活性。其他人已经报道 Gal83 被 Snf1 磷酸化，我们发现 Ubp8 的缺失导致 Gal83 的磷酸化减少，这与 Ubp8 缺失对 Snf1 激酶功能的影响一致。总的来说，我们的数据表明 SAGA 调节 Snf1 的翻译后修饰，以微调基因表达水平。
