Inhibition of v-Abl transformation in 3T3 cells overexpressing different forms of the Abelson interactor protein Abi-1.
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.
Ikeguchi
A
A
Department of Medicine, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.
Yang
H Y
HY
Gao
G
G
Goff
S P
SP
D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins; D002472:Cell Transformation, Viral; D003598:Cytoskeletal Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D016374:Oncogene Proteins v-abl / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection; D018909:src Homology Domains
C513734:Abi1 protein, mouse; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D018398:Homeodomain Proteins; D016374:Oncogene Proteins v-abl; D012333:RNA, Messenger