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.
Caenorhabditis elegans lin-25 functions downstream of let-60 ras in the genetic pathway for the induction of the 1 degrees 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.
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Umeå Center for Molecular Pathogenesis, Umeâ University, SE-901 87 Umeå, Sweden.
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D000595:Amino Acid Sequence; D000818:Animals; D002107:Caenorhabditis / Q000033:anatomy & histology / Q000235:genetics* / Q000502:physiology; D017173:Caenorhabditis elegans / Q000033:anatomy & histology / Q000235:genetics* / Q000502:physiology; D029742:Caenorhabditis elegans Proteins; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D012734:Disorders of Sex Development; D019143:Evolution, Molecular; D005260:Female; D017952:Ganglia, Invertebrate / Q000033:anatomy & histology; D005838:Genotype; D015801:Helminth Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D015801:Helminth Proteins; C117637:LIN-25 protein, C elegans; D014157:Transcription Factors