title: p21CIP1 is not required for the early G2 checkpoint response to ionizing radiation.
abstract: We have previously reported that the immediate G2 checkpoint delay of normal human fibroblasts in response to ionizing radiation is correlated with inhibition of p34CDC2/cyclin B kinase activity. Here, we observed increased amounts of the cyclin-dependent protein kinase inhibitor p21CIP1 associated with p34CDC2/cyclin B protein complexes from irradiated normal human fibroblasts. Since wild-type p53 function is not required for the early G2 checkpoint response to ionizing radiation, we investigated whether a p53-independent induction of p21CIP1 was required for the G2 checkpoint. Early passage human fibroblasts expressing the E6 oncoprotein of human papilloma virus-type 16 (NHF4 E6) were analyzed. It has been demonstrated earlier than inactivation of wild-type p53 function in these cells by E6 protein does not alter their intact early G2 checkpoint response to gamma-rays. p21CIP1 was found to be undetectable in p34CDC2/cyclin B protein complexes and in total extracts from the E6-expressing cells, with or without exposure to ionizing radiation. These data indicate that p21CIP1 is not required for the immediate G2 checkpoint response and is not induced by a p53-independent pathway in G2 phase following exposure to gamma-rays.
authors.affiliation: National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
authors.forename: E N
authors.initials: EN
authors.lastname: Levedakou
authors.forename: W K
authors.initials: WK
authors.lastname: Kaufmann
authors.forename: D A
authors.initials: DA
authors.lastname: Alcorta
authors.forename: D A
authors.initials: DA
authors.lastname: Galloway
authors.forename: R S
authors.initials: RS
authors.lastname: Paules
mesh_terms: D002453:Cell Cycle / Q000502:physiology / Q000528:radiation effects*; D002455:Cell Division; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D016195:G2 Phase / Q000528:radiation effects; D005720:Gamma Rays; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000096:biosynthesis; D027383:Papillomaviridae / Q000235:genetics / Q000378:metabolism; D006656:Protamine Kinase / Q000378:metabolism; D012097:Repressor Proteins; D014162:Transfection
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D012097:Repressor Proteins; D006656:Protamine Kinase