A role of p73 in mitotic exit

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

Research output: Contribution to journalArticle

Abstract

The p53-related p73 proteins regulate developmental processes, cell growth, and DNA damage response. p73 function is regulated by post-translational modifications and protein-protein interactions. At the G2/M transition, p73 is phosphorylated at Thr-86 by the p34cdc2/cyclin B complex; this is associated with its exclusion from condensed chromosomes and loss of DNA binding and transcriptional activation ability. Here we showed that p73 hypo-phosphorylated species reappear during mitotic exit, concomitant with p73 relocalization to telophase nuclei and recovered ability to activate transcription. Functional knock-out of p73 gene expression by small interfering RNAs (siRNAs) alters mitotic progression, yielding an increase of ana-telophase cells, the accumulation of aberrant late mitotic figures, and the appearance of abnormalities in the subsequent interphase. This p73 activity at the M-to-G 1 transition is mediated by its transactivating function because expression of the transcription dominant negative mutant p73DD induces the same mitotic exit phenotype. We also found that the cyclin-dependent kinase inhibitor Kip2/p57 gene is a specific target of p73 regulation during mitotic exit and re-entry into G1. Both knock-out of p73 gene expression by siRNAs and abrogation of p73-dependent transcription by the p73DD mutant abrogate Kip2/p57 increase at the M-to-G1 transition. Moreover, similar abnormalities (e.g. delay in late mitotic stages with the accumulation of aberrant ana-telophase figures, and abnormalities in the following interphase) are observed in cultures in which the expression of Kip2/p57 is abrogated by siRNAs. These results identify a novel p73-Kip2/p57 pathway that coordinates mitotic exit and transition to G1.

Original languageEnglish
Pages (from-to)30354-30360
Number of pages7
JournalJournal of Biological Chemistry
Volume280
Issue number34
DOIs
Publication statusPublished - Aug 26 2005

Fingerprint

Telophase
Transcription
Small Interfering RNA
Interphase
Gene expression
Cyclin-Dependent Kinase Inhibitor p57
Cell Growth Processes
Cyclin B
Gene Expression
Proteins
Cyclin-Dependent Kinases
Reentry
DNA
Cell growth
Post Translational Protein Processing
Chromosomes
Transcriptional Activation
DNA Damage
Genes
Chemical activation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Merlo, P., Fulco, M., Costanzo, A., Mangiacasale, R., Strano, S., Blandino, G., ... Levrero, M. (2005). A role of p73 in mitotic exit. Journal of Biological Chemistry, 280(34), 30354-30360. https://doi.org/10.1074/jbc.M500635200

A role of p73 in mitotic exit. / Merlo, Paola; Fulco, Marcella; Costanzo, Antonio; Mangiacasale, Rosamaria; Strano, Sabrina; Blandino, Giovanni; Taya, Yoichi; Lavia, Patrizia; Levrero, Massimo.

In: Journal of Biological Chemistry, Vol. 280, No. 34, 26.08.2005, p. 30354-30360.

Research output: Contribution to journalArticle

Merlo, P, Fulco, M, Costanzo, A, Mangiacasale, R, Strano, S, Blandino, G, Taya, Y, Lavia, P & Levrero, M 2005, 'A role of p73 in mitotic exit', Journal of Biological Chemistry, vol. 280, no. 34, pp. 30354-30360. https://doi.org/10.1074/jbc.M500635200
Merlo P, Fulco M, Costanzo A, Mangiacasale R, Strano S, Blandino G et al. A role of p73 in mitotic exit. Journal of Biological Chemistry. 2005 Aug 26;280(34):30354-30360. https://doi.org/10.1074/jbc.M500635200
Merlo, Paola ; Fulco, Marcella ; Costanzo, Antonio ; Mangiacasale, Rosamaria ; Strano, Sabrina ; Blandino, Giovanni ; Taya, Yoichi ; Lavia, Patrizia ; Levrero, Massimo. / A role of p73 in mitotic exit. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 34. pp. 30354-30360.
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