p73 is regulated by phosphorylation at the G2/M transition.

Marcella Fulco, Antonio Costanzo, Paola Merlo, Rosamaria Mangiacasale, Sabrina Strano, Giovanni Blandino, Clara Balsano, Patrizia Lavia, Massimo Levrero

Research output: Contribution to journalArticle

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 p34cdc2-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. p34cdc2-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 p34cdc2-cyclin B is associated with negative regulation of its transcriptional activating function.

Original languageEnglish
Pages (from-to)49196-49202
Number of pages7
JournalJournal of Biological Chemistry
Volume278
Issue number49
Publication statusPublished - Dec 5 2003

ASJC Scopus subject areas

  • Biochemistry

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  • Cite this

    Fulco, M., Costanzo, A., Merlo, P., Mangiacasale, R., Strano, S., Blandino, G., Balsano, C., Lavia, P., & Levrero, M. (2003). p73 is regulated by phosphorylation at the G2/M transition. Journal of Biological Chemistry, 278(49), 49196-49202.