Ubiquitin over-expression promotes E6AP autodegradation and reactivation of the p53/MDM2 pathway in HeLa cells

Rita Crinelli, Marzia Bianchi, Michele Menotta, Elisa Carloni, Elisa Giacomini, Marzia Pennati, Mauro Magnani

Research output: Contribution to journalArticle

Abstract

It has been established that intracellular ubiquitin pools are subject to regulatory constrains. Less certain is the mechanism by which the pool of conjugated ubiquitin shift in parallel with total ubiquitin, and how this type of regulation affects the flux of substrates through the pathway. In this study we demonstrate that ubiquitin over-expression promotes the destabilization of the ubiquitin protein ligase E6AP, by a mechanism involving self-ubiquitination, and the stabilization of p53. These results represent the very first evidence that the levels of a ubiquitin ligase can be regulated in vivo by ubiquitin abundance, supporting the idea that a strict interrelationship between pathway component activities and ubiquitin pool size exists. Interestingly, ubiquitin-induced p53 accumulation did not induce cell-cycle arrest, suggesting that although fluctuations of the intracellular ubiquitin content may actively modulate the level of regulatory proteins, this event is not per se sufficient to elicit a cellular response in terms of proliferation.

Original languageEnglish
Pages (from-to)129-145
Number of pages17
JournalMolecular and Cellular Biochemistry
Volume318
Issue number1-2
DOIs
Publication statusPublished - 2008

Keywords

  • E3 ligase activity
  • p53
  • Self-ubiquitination
  • Ubiquitin pools

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology

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    Crinelli, R., Bianchi, M., Menotta, M., Carloni, E., Giacomini, E., Pennati, M., & Magnani, M. (2008). Ubiquitin over-expression promotes E6AP autodegradation and reactivation of the p53/MDM2 pathway in HeLa cells. Molecular and Cellular Biochemistry, 318(1-2), 129-145. https://doi.org/10.1007/s11010-008-9864-8