[Transfection with the E1A and E1B-19kDa oncogenes does not prevent rat embryo fibroblasts from cell cycle arrest after gamma-radiation].
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.
Bulavin
D V
DV
Institute of Cytology, Russian Academy of Sciences, St. Petersburg, 194064 Russia.
Tararova
N D
ND
Brichkina
A I
AI
Aksenova
N D
ND
Pospelov
V A
VA
Pospelova
T V
TV
D017500:Adenovirus E1A Proteins / Q000235:genetics* / Q000378:metabolism / Q000528:radiation effects; D017501:Adenovirus E1B Proteins / Q000235:genetics* / Q000378:metabolism* / Q000528:radiation effects; D000818:Animals; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000235:genetics* / Q000528:radiation effects*; D002478:Cells, Cultured; D019925:Cyclin A / Q000378:metabolism / Q000528:radiation effects; D019927:Cyclin E / Q000378:metabolism / Q000528:radiation effects; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D050759:Cyclin-Dependent Kinase Inhibitor p21; D018844:Cyclin-Dependent Kinases / Q000378:metabolism / Q000528:radiation effects; D016213:Cyclins / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000528:radiation effects; D005720:Gamma Rays; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000528:radiation effects; D011518:Proto-Oncogene Proteins; D051381:Rats; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000528:radiation effects
D017500:Adenovirus E1A Proteins; D017501:Adenovirus E1B Proteins; C493958:Cdkn1a protein, rat; D019925:Cyclin A; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495892:Cdk2 protein, rat; C495903:Cdk4 protein, rat; D051357:Cyclin-Dependent Kinase 2; D051358:Cyclin-Dependent Kinase 4; D018844:Cyclin-Dependent Kinases