TAp73 regulates the spindle assembly checkpoint by modulating BubR1 activity

Richard Tomasini, Katsuya Tsuchihara, Chiharu Tsuda, Suzanne K. Lau, Margareta Wilhelm, Alessandro Ruffini, Ming Sound Tsao, Juan L. Iovanna, Andrea Jurisicova, Gerry Melino, Tak W. Maka

Research output: Contribution to journalArticle

Abstract

The role of various p73 isoforms in tumorigenesis has been controversial. However, as we have recently shown, the generation of TAp73-deficient (TAp73-/-) mice reveals that TAp73 isoforms exert tumor-suppressive functions, indicating an emerging role for Trp-73 in the maintenance of genomic stability. Unlike mice lacking all p73 isoforms, TAp73-/- mice show a high incidence of spontaneous tumors. Moreover, TAp73-/- mice are infertile and produce oocytes exhibiting spindle abnormalities. These data suggest a link between TAp73 activities and the common molecular machinery underlying meiosis and mitosis. Previous studies have indicated that the spindle assembly checkpoint (SAC) complex, whose activation leads to mitotic arrest, also regulates meiosis. In this study, we demonstrate in murine and human cells that TAp73 is able to interact directly with several partners of the SAC complex (Bub1, Bub3, and BubR1). We also show that TAp73 is involved in SAC protein localization and activities. Moreover, we show that decreased TAp73 expression correlates with increases of SAC protein expression in patients with lung cancer. Our results establish TAp73 as a regulator of SAC responses and indicate that TAp73 loss can lead to mitotic arrest defects. Our data suggest that SAC impairment in the absence of functional TAp73 could explain the genomic instability and increased aneuploidy observed in TAp73-deficient cells.

Original languageEnglish
Pages (from-to)797-802
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number3
DOIs
Publication statusPublished - Jan 20 2009

Keywords

  • Bub1
  • Meiosis
  • Mitotic arrest
  • p73
  • Spindle checkpoint

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'TAp73 regulates the spindle assembly checkpoint by modulating BubR1 activity'. Together they form a unique fingerprint.

  • Cite this

    Tomasini, R., Tsuchihara, K., Tsuda, C., Lau, S. K., Wilhelm, M., Ruffini, A., Tsao, M. S., Iovanna, J. L., Jurisicova, A., Melino, G., & Maka, T. W. (2009). TAp73 regulates the spindle assembly checkpoint by modulating BubR1 activity. Proceedings of the National Academy of Sciences of the United States of America, 106(3), 797-802. https://doi.org/10.1073/pnas.0812096106