Constitutive activation of cyclin B1-associated cdc2 kinase overrides p53-mediated G2-M arrest

Recent studies have suggested that p53 regulates the G2 checkpoint in the cell cycle and that this function is required for the maintenance of genomic integrity. In this study, we investigated a regulatory role of p53 specifically in G2-M transition. Human bladder carcinoma cells lacking functional...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2000-02, Vol.60 (3), p.542-545
Main Authors: PARK, M, CHAE, H.-D, YUN, J, JUNG, M, KIM, Y.-S, KIM, S.-H, MOON HI HAN, SHIN, D. Y
Format: Article
Language:English
Subjects:
Biological and medical sciences
CDC2 Protein Kinase - physiology
Cell cycle, cell proliferation
Cell physiology
Cyclin B - physiology
Cyclin B1
Enzyme Activation
Fundamental and applied biological sciences. Psychology
G2 Phase
Humans
Mitosis
Molecular and cellular biology
Tumor Cells, Cultured
Tumor Suppressor Protein p53 - physiology
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Summary:Recent studies have suggested that p53 regulates the G2 checkpoint in the cell cycle and that this function is required for the maintenance of genomic integrity. In this study, we investigated a regulatory role of p53 specifically in G2-M transition. Human bladder carcinoma cells lacking functional p53 were synchronized at G1-S, which is preceded by p53-mediated G1 arrest. p53 expression in the synchronized cells was induced by infection with a recombinant adenovirus that encodes p53. After release from the G1-S arrest, the cells progressed to S-phase and G2 but failed to enter mitosis. Biochemical analysis showed that p53 inhibits cell cycle-dependent expression of cdc2 and cyclin B1 and consequently inhibits cdc2 kinase. The role of cyclin B1-associated cdc2 kinase in p53-mediated G2-M arrest was further investigated by expression of both cyclin B1 and cdc2AF, in which inhibitory phosphorylation sites were substituted. The cells expressing both cdc2AF and cyclin B1 showed a constitutive activation of cdc2 kinase during cell cycle progression and passed through G2-M regardless of p53 expression. Therefore, inactivation of cdc2 kinase through cdc2 and cyclin B1 repression is an essential step in p53-mediated G2-M arrest.
ISSN:0008-5472
1538-7445