当前位置: Nature » 蛋白&蛋白质组学 » 正文


摘要 : 现在,Michael Green及同事报告说,TRIM37能使组蛋白H2A发生“单泛素化”,通过与polycomb复合物PRC2相结合来在基因调控中发挥功能。 TRIM37被认为通过改变PRC2的特异性和帮助肿瘤抑制因子及其他基因的沉默来促进转变。


 RING finger蛋白TRIM37是通过在某些乳腺癌中被放大的一个基因编码的,但其功能过去并不知道。现在,Michael Green及同事报告说,TRIM37能使组蛋白H2A发生“单泛素化”,通过与polycomb复合物PRC2相结合来在基因调控中发挥功能。 TRIM37被认为通过改变PRC2的特异性和帮助肿瘤抑制因子及其他基因的沉默来促进转变。


TRIM37 is a new histone H2A ubiquitin ligase and breast cancer oncoprotein

Sanchita Bhatnagar, Claude Gazin, Lynn Chamberlain, Jianhong Ou, Xiaochun Zhu,Jogender S. Tushir, Ching-Man Virbasius, Ling Lin, Lihua J. Zhu, Narendra Wajapeyee &Michael R. Green

The TRIM37 (also known as MUL) gene is located in the 17q23 chromosomal region, which is amplified in up to ~40% of breast cancers1. TRIM37 contains a RING finger domain, a hallmark of E3 ubiquitin ligases2, but its protein substrate(s) is unknown. Here we report that TRIM37 mono-ubiquitinates histone H2A, a chromatin modification associated with transcriptional repression3. We find that in human breast cancer cell lines containing amplified 17q23, TRIM37 is upregulated and, reciprocally, the major H2A ubiquitin ligase RNF2 (also known as RING1B)3, 4 is downregulated. Genome-wide chromatin immunoprecipitation (ChIP)-chip experiments in 17q23-amplified breast cancer cells identified many genes, including multiple tumour suppressors, whose promoters were bound by TRIM37 and enriched for ubiquitinated H2A. However, unlike RNF2, which is a subunit of polycomb repressive complex 1 (PRC1)3, 4, 5, we find that TRIM37 associates with polycomb repressive complex 2 (PRC2). TRIM37, PRC2 and PRC1 are co-bound to specific target genes, resulting in their transcriptional silencing. RNA-interference-mediated knockdown of TRIM37 results in loss of ubiquitinated H2A, dissociation of PRC1 and PRC2 from target promoters, and transcriptional reactivation of silenced genes. Knockdown of TRIM37 in human breast cancer cells containing amplified 17q23 substantially decreases tumour growth in mouse xenografts. Conversely, ectopic expression of TRIM37 renders non-transformed cells tumorigenic. Collectively, our results reveal TRIM37 as an oncogenic H2A ubiquitin ligase that is overexpressed in a subset of breast cancers and promotes transformation by facilitating silencing of tumour suppressors and other genes.(doi: 10.1038/nature13955

对应Nature杂志: 2014年12月04日Nature杂志精选

来源: Nature中文 浏览次数:213


RSS订阅 - 填写您的邮件地址,订阅我们的精彩内容: - 网站地图
网站联系电话:020-87540820 备案号:粤ICP备11050685号-8 增值电信业务经营许可证:粤B2-20120479
©2011-2015 生物帮 All rights reserved.