Control of p53 multimerization by Ubc13 is JNK-regulated

Ivan Topisirovic, Gustavo J. Gutierrez, Meifan Chen, Ettore Appella, Katherine L.B. Borden, Ze'ev A. Ronai

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The p53 tumor suppressor protein is a key regulator of cellular proliferation and survival whose function is tightly regulated at the levels of transcription and protein stability. Here, we unveil the fine control of p53 on translationally active polysomes. We have previously reported that Ubc13, an E2 ubiquitin-conjugating enzyme, directly regulates p53 localization and transcriptional activity. We now demonstrate that the association of p53 and Ubc13 on polysomes requires ongoing translation and results in p53 ubiquitination that interferes with its tetramerization. JNK phosphorylation of p53 at Threonine 81 occurring on polysomes is required for the dissociation of Ubc13 from p53, leading to p53 multimerization and transcriptional activation. Inhibition of JNK activity or expression of a nonphosphorylatable mutant of p53 maintains an Ubc13-p53 complex that inhibits p53 multimerization. Our findings reveal a layer in the regulation of p53 multimerization that requires the concerted action of JNK and Ubc13 on polysome-bound p53.

Original languageEnglish (US)
Pages (from-to)12676-12681
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number31
DOIs
StatePublished - Aug 4 2009

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Polyribosomes
Ubiquitin-Conjugating Enzymes
Tumor Suppressor Protein p53
Protein Stability
Ubiquitination
Threonine
Transcriptional Activation
Phosphorylation
Cell Proliferation

Keywords

  • Polysomes
  • Ubiquitin

ASJC Scopus subject areas

  • General

Cite this

Control of p53 multimerization by Ubc13 is JNK-regulated. / Topisirovic, Ivan; Gutierrez, Gustavo J.; Chen, Meifan; Appella, Ettore; Borden, Katherine L.B.; Ronai, Ze'ev A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 31, 04.08.2009, p. 12676-12681.

Research output: Contribution to journalArticle

Topisirovic, Ivan ; Gutierrez, Gustavo J. ; Chen, Meifan ; Appella, Ettore ; Borden, Katherine L.B. ; Ronai, Ze'ev A. / Control of p53 multimerization by Ubc13 is JNK-regulated. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 31. pp. 12676-12681.
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