Heat shock induces transient p53-dependent cell cycle arrest at G1/S.
Heat shock (43 degrees C, 45 min) induced transient nuclear accumulation of p53 in primary human fibroblasts without any clonogenically toxic effects. The accumulation of p53 reached a maximal level 3 approximately 5 h after heat shock, and returned to the basal level within 12 h. Following the increase in p53 level, cell cycle arrest at G1/S was observed in normal fibroblasts, whereas neither nuclear accumulation of p53 nor cell cycle arrest were observed in HeLa cells. By comparing cell cycle patterns of heat-treated mouse cells with different genotypes at the p53 locus (+/+, +/-, -/-), the observed cell cycle arrest at G1/S was demonstrated to be p53-dependent. Cell cycle arrest in normal human fibroblasts continued for nearly 24 h, resulting in a one day delay of cell growth compared with non-treated cells. Following enhancement of the p53 level, the amount of p21/WAF1/ CIP1 increased, and the high level of p21 was sustained for almost one day in a cell cycle-independent manner, suggesting the involvement of p21 in the inhibition of cell cycle progression by heat shock.
Nitta
M
M
Institute of Molecular Embryology and Genetics, Department of Obstetrics and Gynecology, Kumamoto University School of Medicine, Japan.
Okamura
H
H
Aizawa
S
S
Yamaizumi
M
M
D000818:Animals; D002453:Cell Cycle / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D016193:G1 Phase / Q000235:genetics; D006358:Hot Temperature / Q000009:adverse effects*; D006801:Humans; D051379:Mice; D016196:S Phase / Q000235:genetics; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53