Harrison Melissa M, Ceol Craig J, Lu Xiaowei, Horvitz H Robert
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Proc Natl Acad Sci U S A. 2006 Nov 7;103(45):16782-7. doi: 10.1073/pnas.0608461103. Epub 2006 Oct 30.
The Caenorhabditis elegans synthetic multivulva (synMuv) genes act redundantly to antagonize the specification of vulval cell fates, which are promoted by an RTK/Ras pathway. At least 26 synMuv genes have been genetically identified, several of which encode proteins with homologs that act in chromatin remodeling or transcriptional repression. Here we report the molecular characterization of two synMuv genes, lin-37 and lin-54. We show that lin-37 and lin-54 encode proteins in a complex with at least seven synMuv proteins, including LIN-35, the only C. elegans homolog of the mammalian tumor suppressor Rb. Biochemical analyses of mutants suggest that LIN-9, LIN-53, and LIN-54 are required for the stable formation of this complex. This complex is distinct from a second complex of synMuv proteins with a composition similar to that of the mammalian Nucleosome Remodeling and Deacetylase complex. The class B synMuv complex we identified is evolutionarily conserved and likely functions in transcriptional repression and developmental regulation.
秀丽隐杆线虫的合成多阴门(synMuv)基因通过冗余作用拮抗由受体酪氨酸激酶/ Ras途径促进的阴门细胞命运的特化。已通过遗传学方法鉴定出至少26个synMuv基因,其中几个基因编码的蛋白质具有在染色质重塑或转录抑制中起作用的同源物。在此,我们报告两个synMuv基因lin-37和lin-54的分子特征。我们表明,lin-37和lin-54编码的蛋白质与至少七种synMuv蛋白质形成复合物,其中包括LIN-35,它是哺乳动物肿瘤抑制因子Rb在秀丽隐杆线虫中唯一的同源物。对突变体的生化分析表明,LIN-9、LIN-53和LIN-54是该复合物稳定形成所必需的。该复合物不同于另一种synMuv蛋白质复合物,其组成与哺乳动物核小体重塑和去乙酰化酶复合物相似。我们鉴定出的B类synMuv复合物在进化上是保守的,可能在转录抑制和发育调控中发挥作用。