[Yoon CH] positive clone restores Vul phenotype, suppresses hyperinduction. [injected into animals of the genotype let-23(sy1); sli-1(sy143) and let-23(sy1); sli-1(sy129)].
[C.elegansII] sy143 : suppressor of vulvaless phenotype of let-23 hypomorph; other let-23 defects suppressed, but not sterility; multivulva phenotype in combination with unc-101; low penetrance head morphology defect in let-23(+) background. sy143/Df similar. OA>10: sy263 (weaker), sy129 etc. Cloned: encodes homolog of mammalian oncogene c-cbl (55% identity over 390 aa, containing RING finger motif. sy129 missense. [Jongeward et al. 1995; Yoon et al. 1995; PS]
sli-1 encodes the C. elegans ortholog of the Cbl family of ubiquitin ligases; sli-1 was originally identified as a suppressor of a hypomorphic mutation in LET-23/EGFR and thus, is predicted to function as a negative regulator of LET-23-mediated signaling; genetic analyses place sli-1 upstream of let-60/Ras; a chimeric protein substituting human SH2 and RING finger domains for those of SLI-1 is partially functional for regulating vulval differentiation in vivo; sli-1(RNAi) in the background of a let-756/FGF mutant results in slow growing animals.
Predicted to enable SH3 domain binding activity; receptor tyrosine kinase binding activity; and ubiquitin protein ligase activity. Involved in negative regulation of vulval development. Predicted to be located in membrane raft and plasma membrane. Expressed in several structures, including anal depressor muscle; body wall musculature; distal tip cell; head; and intestine. Human ortholog(s) of this gene implicated in several diseases, including gastrointestinal system cancer (multiple); hematologic cancer (multiple); and lung squamous cell carcinoma. Is an ortholog of human CBL (Cbl proto-oncogene); CBLB (Cbl proto-oncogene B); and CBLC (Cbl proto-oncogene C).