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P73 Is Regulated by Phosphorylation at the G[sub 2]/M Transition.
- Source :
-
Journal of Biological Chemistry . 12/5/2003, Vol. 278 Issue 49, p49196-49202. 7p. 3 Color Photographs, 10 Black and White Photographs, 2 Charts, 3 Graphs. - Publication Year :
- 2003
-
Abstract
- p73 is a p53 paralog that encodes proapoptotic (transactivation-competent (TA)) and antiapoptotic (dominant negative) isoforms. TAp73 transcription factors mediate cell cycle arrest and/or apoptosis in response to DNA damage and are involved in developmental processes in the central nervous system and the immune system, p73 proteins may also play a role in the regulation of cell growth. Indeed, p73 expression is itself modulated during the cell cycle and TAp73 proteins accumulate in S phase cells. In addition, the function of p73 proteins is also regulated by post-translational modifications and protein-protein interactions in different cellular and pathophysiological contexts. Here we show that p73 is a physiological target of the p34[sup cdc2]-cyclin B mitotic kinase complex in vivo. Both p73β and p73α isoforms are hyperphosphorylated in normal mitotic cells and during mitotic arrest induced by microtubule-targeting drugs, p34[sup cdc2]-cyclin B phosphorylates and associates with p73 in vivo, which results in a decreased ability of p73 to both bind DNA and activate transcription in mitotic cells. Indeed, p73 is excluded from condensed chromosomes in meta- and anaphase, redistributes throughout the mitotic cytoplasm, and unlike p53, shows no association with centrosomes. Together these results indicate that M phase-specific phosphorylation of p73 by p34[sup cdc2]-cyclin B is associated with negative regulation of its transcriptional activating function. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00219258
- Volume :
- 278
- Issue :
- 49
- Database :
- Academic Search Index
- Journal :
- Journal of Biological Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 11897741
- Full Text :
- https://doi.org/10.1074/jbc.M304921200