Perturbation of 60 S ribosomal biogenesis results in ribosomal protein L5- and L11-dependent p53 activation

Xiao-Xin Sun, Yue Gang Wang, Dimitris P. Xirodimas, Mushui Dai

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Ribosomal proteins play an important role in p53 activation in response to nucleolar stress. Multiple ribosomal proteins, including L5, L11, L23, and S7, have been shown to bind to and inhibit MDM2, leading to p53 activation. However, it is not clear whether ribosomal protein regulation of MDM2 is specific to some, but not all ribosomal proteins. Here we show that L29 and L30, two ribosomal proteins from the 60 S ribosomal subunit, do not bind to MDM2 and do not inhibit MDM2-mediated p53 suppression, indicating that the ribosomal protein regulation of the MDM2-p53 feedback loop is specific. Interestingly, direct perturbation of the 60 S ribosomal biogenesis by knocking down either L29 or L30 drastically induced the level and activity of p53, leading to p53-depedent cell cycle arrest. This p53 activation was drastically inhibited by knockdown of L11 or L5. Consistently, knockdown of L29 or L30 enhanced the interaction of MDM2 with L11 and L5 and markedly inhibited MDM2-mediated p53 ubiquitination, suggesting that direct perturbation of 60 S ribosomal biogenesis activates p53 via L11- and L5-mediated MDM2 suppression. Mechanistically, knockdown of L30 or L29 significantly increased the NEDDylation and nuclear retention of L11. Knocking down endogenous NEDD8 suppressed p53 activation induced by knockdown of L30. These results demonstrate that NEDDylation of L11 plays a critical role in mediating p53 activation in response to perturbation of ribosomal biogenesis.

Original languageEnglish (US)
Pages (from-to)25812-25821
Number of pages10
JournalJournal of Biological Chemistry
Volume285
Issue number33
DOIs
StatePublished - Aug 13 2010

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L 30
Ribosomal Proteins
Chemical activation
ethyl-2-methylthio-4-methyl-5-pyrimidine carboxylate
Ribosome Subunits
Ubiquitination
Protein S
Cell Cycle Checkpoints
ribosomal protein L5
ribosomal protein L11
Cells
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ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Perturbation of 60 S ribosomal biogenesis results in ribosomal protein L5- and L11-dependent p53 activation. / Sun, Xiao-Xin; Wang, Yue Gang; Xirodimas, Dimitris P.; Dai, Mushui.

In: Journal of Biological Chemistry, Vol. 285, No. 33, 13.08.2010, p. 25812-25821.

Research output: Contribution to journalArticle

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