[HS1 and EMS1].
Both HS1 (hematopoiesis specific) and EMS1/ cortactin belong to a growing family of cytoskeletal SH3 proteins. Most proteins in this family, except for alpha-spectrin, contain a single SH3 domain at the C-terminus, and an F-actin binding domain (s) at the N-terminus. The main reason why EMS1 initially attracted great attention among molecular oncologists is the amplification and over-expression of EMS1 gene in mammary tumors. However, our recent study on HS1 suggests that EMS1 is a tumor suppressor rather than a proto-oncoprotein. First of all, full-length HS1 of 486 amino acids suppresses the malignant transformation caused by oncogenic Ras mutants such as v-Ha-Ras. Second, for its anti-oncogenicity, HS1 requires the C-terminal SH3 domain, and the N-terminal actin-binding motifs, in addition to two phosphorylatable Tyr residues at positions 378 and 397. Third, EMS1 shares with HS1 80% sequence identity in the C-terminal SH3 domain, and 70% identity in the N-terminal actin-binding motifs, and contains these two Tyr residues, all of which are required for the anti-oncogenicity of HS1. Lastly, overexpression of EMS1 does not transform normal cells, and rather disfavors their growth. Among several actin-binding tumor suppressors, HS1 is the first tumor suppressor whose actin-binding has been shown to be essential for its anti-oncogenicity.
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Ludwig Institute for Cancer Research, Melbourne.
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001798:Blood Proteins / Q000737:chemistry / Q000502:physiology; D051356:Cortactin; D011905:Genes, ras; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000737:chemistry; D009363:Neoplasm Proteins / Q000737:chemistry / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D001798:Blood Proteins; C495868:CTTN protein, human; D051356:Cortactin; C495869:Cttn protein, mouse; C061909:HCLS1 protein, human; D008840:Microfilament Proteins; D009363:Neoplasm Proteins