Identification of KIN (KIN17), a human gene encoding a nuclear DNA-binding protein, as a novel component of the TP53-independent response to ionizing radiation.
Ionizing radiation elicits a genetic response in human cells that allows cell survival. The human KIN (also known as KIN17) gene encodes a 45-kDa nuclear DNA-binding protein that participates in the response to UVC radiation and is immunologically related to the bacterial RecA protein. We report for the first time that ionizing radiation and bleomycin, a radiomimetic drug, which produce single- and double-strand breaks, increased expression of KIN in human cells established from tumors, including MeWo melanoma, MCF7 breast adenocarcinoma, and ATM+ GM3657 lymphoblast cells. KIN expression increased rapidly in a dose-dependent manner after irradiation. Under the same conditions, several genes controlled by TP53 were induced with kinetics similar to that of KIN. Using the CDKN1A gene as a marker of TP53 responsiveness, we analyzed the up-regulation of KIN and showed that is independent of the status of TP53 and ATM. In contrast, the presence of a dominant mutant for activating transcription factor 2 (ATF2) completely abolished the up-regulation of KIN. Our results suggest a role for ATF2 in the TP53-independent increase in KIN expression after gamma irradiation.
Masson
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C
Laboratoire de Génétique de la Radiosensibilité, Direction des Sciences du Vivant, Centre d'Etudes de Fontenay-aux-Roses, CEA, 60-68, Avenue du Général-Leclerc, B.P. no. 6, 92265 Fontenay-aux-Roses Cedex, France.
Menaa
F
F
Pinon-Lataillade
G
G
Frobert
Y
Y
Radicella
J P
JP
Angulo
J F
JF
D051698:Activating Transcription Factor 2; D001761:Bleomycin / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics*; D005720:Gamma Rays; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D006801:Humans; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors / Q000502:physiology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; C493956:CDKN1A protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; C489487:KIN protein, human; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D001761:Bleomycin