Caenorhabditis elegans lin-25: A Study of Its Role in Multiple Cell Fate Specification Events Involving Ras and the Identification and Characterization of Evolutionarily Conserved Domains

Corresponding author: Simon Tuck, UCMP, Byggnad 6L, Umeå University, SE-901 87 Umeå, Sweden., simon.tuck{at}ucmp.umu.se (E-mail)

Communicating editor: R. K. HERMAN

Caenorhabditis elegans lin-25 functions downstream of let-60 ras in the genetic pathway for the induction of the 1° cell fate during vulval development and encodes a novel 130-kD protein. The biochemical activity of LIN-25 is presently unknown, but the protein appears to function together with SUR-2, whose human homologue binds to Mediator, a protein complex required for transcriptional regulation. We describe here experiments that indicate that, besides its role in vulval development, lin-25 also participates in the fate specification of a number of other cells in the worm that are known to require Ras-mediated signaling. We also describe the cloning of a lin-25 orthologue from C. briggsae. Sequence comparisons suggest that the gene is evolving relatively rapidly. By characterizing the molecular lesions associated with 10 lin-25 mutant alleles and by assaying in vivo the activity of mutants lin-25 generated in vitro, we have identified three domains within LIN-25 that are required for activity or stability. We have also identified a sequence that is required for efficient nuclear translocation. We discuss how lin-25 might act in cell fate specification in C. elegans within the context of models for lin-25 function in cell identity and cell signaling.

This article has been cited by other articles:

				R. M. Howard and M. V. Sundaram C. elegans EOR-1/PLZF and EOR-2 positively regulate Ras and Wnt signaling and function redundantly with LIN-25 and the SUR-2 Mediator component Genes & Dev., July 15, 2002; 16(14): 1815 - 1827. [Abstract] [Full Text] [PDF]

				C. E. Rocheleau, R. M. Howard, A. P. Goldman, M. L. Volk, L. J. Girard, and M. V. Sundaram A lin-45 raf Enhancer Screen Identifies eor-1, eor-2 and Unusual Alleles of Ras Pathway Genes in Caenorhabditis elegans Genetics, May 1, 2002; 161(1): 121 - 131. [Abstract] [Full Text] [PDF]