在秀丽隐杆线虫的外阴发育过程中，dpl-1 DP和efl-1 E2F与lin-35 Rb共同作用以拮抗Ras信号通路。

dpl-1 DP and efl-1 E2F act with lin-35 Rb to antagonize Ras signaling in C. elegans vulval development.

作者信息

Ceol C J, Horvitz H R

机构信息

Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

出版信息

Mol Cell. 2001 Mar;7(3):461-73. doi: 10.1016/s1097-2765(01)00194-0.

DOI:10.1016/s1097-2765(01)00194-0

PMID:11463372

Abstract

The synthetic multivulva (synMuv) genes define two functionally redundant pathways that antagonize RTK/Ras signaling during Caenorhabditis elegans vulval induction. The synMuv gene lin-35 encodes a protein similar to the mammalian tumor suppressor pRB and has been proposed to act as a transcriptional repressor. Studies using mammalian cells have shown that pRB can prevent cell cycle progression by inhibiting DP/E2F-mediated transcriptional activation. We identified C. elegans genes that encode proteins similar to DP or E2F. Loss-of-function mutations in two of these genes, dpl-1 DP and efl-1 E2F, caused the same vulval abnormalities as do lin-35 Rb loss-of-function mutations. We propose that rather than being inhibited by lin-35 Rb, dpl-1 DP and efl-1 E2F act with lin-35 Rb in transcriptional repression to antagonize RTK/Ras signaling during vulval development.

摘要

合成多外阴（synMuv）基因定义了两条功能冗余的途径，它们在秀丽隐杆线虫外阴诱导过程中拮抗RTK/Ras信号传导。synMuv基因lin-35编码一种与哺乳动物肿瘤抑制因子pRB相似的蛋白质，并被认为作为转录抑制因子发挥作用。使用哺乳动物细胞的研究表明，pRB可通过抑制DP/E2F介导的转录激活来阻止细胞周期进程。我们鉴定出了秀丽隐杆线虫中编码与DP或E2F相似蛋白质的基因。其中两个基因dpl-1（DP）和efl-1（E2F）的功能缺失突变导致了与lin-35（Rb）功能缺失突变相同的外阴异常。我们提出，dpl-1（DP）和efl-1（E2F）并非被lin-35（Rb）抑制，而是在转录抑制过程中与lin-35（Rb）共同作用，以拮抗外阴发育过程中的RTK/Ras信号传导。