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The nuclear tyrosine kinase c-Abl negatively regulates cell growth.
c-Abl is a tyrosine kinase localized primarily in the nucleus. Previous assays for abl function rely on cellular transformation by abl mutants, which are cytoplasmic. Using a conditional overexpression strategy, we have developed a functional assay for c-abl. Overexpression of c-abl inhibits growth by causing cell cycle arrest. Growth suppression requires tyrosine kinase activity, nuclear localization, and an intact SH2 domain. Overexpression of dominant negative c-abl disrupts cell cycle control and enhances transformation by tyrosine kinases, G proteins, and transcription factor oncogenes. These findings suggest that c-abl acts as a negative regulator of cell growth. This growth suppressive activity is functionally similar to that of tumor suppressor genes such as p53 and Rb.[1]References
- The nuclear tyrosine kinase c-Abl negatively regulates cell growth. Sawyers, C.L., McLaughlin, J., Goga, A., Havlik, M., Witte, O. Cell (1994) [Pubmed]
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