Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Aberrant expression of nucleostemin activates p53 and induces cell cycle arrest via inhibition of MDM2.

The nucleolar protein nucleostemin (NS) is essential for cell proliferation and early embryogenesis. Both depletion and overexpression of NS reduce cell proliferation. However, the mechanisms underlying this regulation are still unclear. Here, we show that NS regulates p53 activity through the inhibition of MDM2. NS binds to the central acidic domain of MDM2 and inhibits MDM2-mediated p53 ubiquitylation and degradation. Consequently, ectopic overexpression of NS activates p53, induces G(1) cell cycle arrest, and inhibits cell proliferation. Interestingly, the knockdown of NS by small interfering RNA also activates p53 and induces G(1) arrest. These effects require the ribosomal proteins L5 and L11, since the depletion of NS enhanced their interactions with MDM2 and the knockdown of L5 or L11 abrogated the NS depletion-induced p53 activation and cell cycle arrest. These results suggest that a p53-dependent cell cycle checkpoint monitors changes of cellular NS levels via the impediment of MDM2 function.

Pubmed ID: 18426907 RIS Download

Mesh terms: Carrier Proteins | Cell Cycle | Cell Line, Tumor | Cell Nucleolus | Cell Proliferation | G1 Phase | GTP-Binding Proteins | Humans | Nuclear Proteins | Protein Binding | Protein Processing, Post-Translational | Protein Structure, Tertiary | Proto-Oncogene Proteins c-mdm2 | RNA, Small Interfering | Ribosomal Proteins | Tumor Suppressor Protein p53 | Ubiquitination

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NCI NIH HHS, Id: CA079721
  • Agency: NCI NIH HHS, Id: CA095441
  • Agency: NCI NIH HHS, Id: CA93614
  • Agency: NCI NIH HHS, Id: K99 CA127134
  • Agency: NCI NIH HHS, Id: K99 CA127134-01
  • Agency: NCI NIH HHS, Id: K99-CA127134
  • Agency: NCI NIH HHS, Id: R00 CA127134

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.