Interplay between ribosomal protein S27a and MDM2 protein in p53 activation in response to ribosomal stress

Xiao-Xin Sun, Tiffany DeVine, Kishore B. Challagundla, Mushui Dai

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Ribosomal proteins play a critical role in tightly coordinating p53 signaling with ribosomal biogenesis. Several ribosomal proteins have been shown to induce and activate p53 via inhibition of MDM2. Here, we report that S27a, a small subunit ribosomal protein synthesized as an 80-amino acid ubiquitin C-terminal extension protein (CEP80), functions as a novel regulator of the MDM2-p53 loop. S27a interacts with MDM2 at the central acidic domain of MDM2 and suppresses MDM2-mediated p53 ubiquitination, leading to p53 activation and cell cycle arrest. Knockdown of S27a significantly attenuates the p53 activation in cells in response to treatment with ribosomal stress-inducing agent actinomycin D or 5-fluorouracil. Interestingly, MDM2 in turn ubiquitinates S27a and promotes proteasomal degradation of S27a in response to actinomycin D treatment, thus forming a mutual-regulatory loop. Altogether, our results reveal that S27a plays a non-redundant role in mediating p53 activation in response to ribosomal stress via interplaying with MDM2.

Original languageEnglish (US)
Pages (from-to)22730-22741
Number of pages12
JournalJournal of Biological Chemistry
Volume286
Issue number26
DOIs
StatePublished - Jul 1 2011

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Ribosomal Proteins
Chemical activation
Dactinomycin
Ubiquitin C
Proteins
Ubiquitination
Cell Cycle Checkpoints
Fluorouracil
Cells
Amino Acids
Degradation
ribosomal protein S27a

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Interplay between ribosomal protein S27a and MDM2 protein in p53 activation in response to ribosomal stress. / Sun, Xiao-Xin; DeVine, Tiffany; Challagundla, Kishore B.; Dai, Mushui.

In: Journal of Biological Chemistry, Vol. 286, No. 26, 01.07.2011, p. 22730-22741.

Research output: Contribution to journalArticle

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AU - Dai, Mushui

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