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(cdc2)-cyclin B mitotic kinase complex in vivo. Both p73beta and p73alpha isoforms are hyperphosphorylated in normal mitotic cells and during mitotic arrest induced by microtubule-targeting drugs. p34(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(cdc2)- cyclin B is associated with negative regulation of its transcriptional activating function.
p73 is regulated by phosphorylation at the G2/M transition / M., Fulco; A., Costanzo; P., Merlo; R., Mangiacasale; S., Strano; G., Blandino; C., Balsano; P., Lavia; Levrero, Massimo. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - STAMPA. - 278:49(2003), pp. 49196-49202. [10.1074/jbc.m304921200]
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|Titolo:||p73 is regulated by phosphorylation at the G2/M transition|
|Data di pubblicazione:||2003|
|Citazione:||p73 is regulated by phosphorylation at the G2/M transition / M., Fulco; A., Costanzo; P., Merlo; R., Mangiacasale; S., Strano; G., Blandino; C., Balsano; P., Lavia; Levrero, Massimo. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - STAMPA. - 278:49(2003), pp. 49196-49202. [10.1074/jbc.m304921200]|
|Appartiene alla tipologia:||01a Articolo in rivista|