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  • Title: [Transfection with the E1A and E1B-19kDa oncogenes does not prevent rat embryo fibroblasts from cell cycle arrest after gamma-radiation].
    Author: Bulavin DV, Tararova ND, Brichkina AI, Aksenova ND, Pospelov VA, Pospelova TV.
    Journal: Mol Biol (Mosk); 2002; 36(1):58-65. PubMed ID: 11862714.
    Abstract:
    Introduction of the E1A early region of the human adenovirus type 5 impairs the ability of mammalian cells to arrest the cell cycle at G1/S after damage. Two-parameter fluorescent-activated cell sorting (FACS) with iododeoxyuridine revealed the radiation-induced G1/S arrest in rat embryo fibroblasts transformed with the complementing E1A + E1B-19 kDa oncogenes. This was due to selective inhibition of CycIE/Cdk2-associated kinase activity, while activities of type 2 kinase and of CyclA/Cdk2 complexes remained unchanged. The inhibitor of G1-phase cyclin kinases, p21/Waf1, was accumulated and interacted with target kinases both in normal and in transformed cells after irradiation. As shown by immunoprecipitation, p21/Waf1 formed complexes with the E1A on coproducts in the transformants, which possibly accounted for its functional inactivation. Kinase modification in cyclin-kinase complexes was assumed to play a key role in regulation of cyclin-dependent kinases in the transformants with inactivated p21/Waf1.
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