Physical and functional interaction between ribosomal protein L11 and the tumor suppressor ARF

Mu Shui Dai, Kishore B. Challagundla, Xiao Xin Sun, Lakshmi Reddy Palam, Shelya X. Zeng, Ronald Wek, Hua Lu

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The ARF tumor suppressor protein activates p53 in response to oncogenic stress, whereas ribosomal protein L11 induces p53 following ribosomal stress. Both proteins bind to central, albeit non-overlapping, regions of MDM2 and suppress MDM2 activity toward p53. However, it is not known whether the two pathways are functionally connected. Here we show that ARF directly binds to L11 in vitro and in cells, which then forms a complex with MDM2 and p53. L11 collaboratively enhances ARF-induced p53 transcriptional activity and cell cycle arrest. Supporting these results, knocking down L11 reduces ARF-mediated p53 accumulation and alleviates ARF-induced cell cycle arrest. Interestingly, overexpression of ARF increases the levels of ribosome-free L11 and enhances the interaction of L11 with MDM2 and p53. These results demonstrate that ARF activates p53, at least partly by induction of ribosomal stress, which results in L11 suppression of MDM2, and suggest that the ARFMDM2-p53 and the L11-MDM2-p53 pathways are functionally connected.

Original languageEnglish
Pages (from-to)17120-17129
Number of pages10
JournalJournal of Biological Chemistry
Volume287
Issue number21
DOIs
StatePublished - May 18 2012

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Cell Cycle Checkpoints
Tumors
Activity Cycles
Tumor Suppressor Protein p53
Ribosomes
Cells
Neoplasms
Proteins
ribosomal protein L11
In Vitro Techniques

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Physical and functional interaction between ribosomal protein L11 and the tumor suppressor ARF. / Dai, Mu Shui; Challagundla, Kishore B.; Sun, Xiao Xin; Palam, Lakshmi Reddy; Zeng, Shelya X.; Wek, Ronald; Lu, Hua.

In: Journal of Biological Chemistry, Vol. 287, No. 21, 18.05.2012, p. 17120-17129.

Research output: Contribution to journalArticle

Dai, Mu Shui ; Challagundla, Kishore B. ; Sun, Xiao Xin ; Palam, Lakshmi Reddy ; Zeng, Shelya X. ; Wek, Ronald ; Lu, Hua. / Physical and functional interaction between ribosomal protein L11 and the tumor suppressor ARF. In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 21. pp. 17120-17129.
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