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Inhibition of v-Abl transformation in 3T3 cells overexpressing different forms of the Abelson interactor protein Abi-1

Abstract

The abi-1 gene encodes a protein that binds and is phosphorylated by the Abelson protein tyrosine kinase. Constructs expressing a full-length abi-1 cDNA, and a smaller cDNA arising from an alternatively spliced form, were generated and tested for their effect on transformation of NIH3T3 cells by the Abelson murine leukemia virus. Overexpression of both forms of the protein strongly inhibited transformation by the wild-type P160 strain of the virus, but not by the non-interacting mutant P90A strain. The inhibition required the SH3 domain of Abi-1, suggesting that a direct interaction was required for the effect. Rare breakthrough P160 transformants of the Abi-1 overexpressing lines were found to have downregulated Abi-1 protein levels by a post-transcriptional mechanism.

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Acknowledgements

This work was supported by Public Health Service grant P01 CA 23767 from the National Cancer Institute. H-Y Yang and G Gao are Associates, and SP Goff is an Investigator of the Howard Hughes Medical Institute.

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Ikeguchi, A., Yang, HY., Gao, G. et al. Inhibition of v-Abl transformation in 3T3 cells overexpressing different forms of the Abelson interactor protein Abi-1. Oncogene 20, 4926–4934 (2001). https://doi.org/10.1038/sj.onc.1204502

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