spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online 25 November 2008
doi: 10.1242/jcs.037952

Journal of Cell Science 121, 4037-4046 (2008)
Published by The Company of Biologists 2008
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplementary Material
Right arrow All Versions of this Article:
jcs.037952v1
121/24/4037    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Meng, L.
Right arrow Articles by Tsai, R. Y. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Meng, L.
Right arrow Articles by Tsai, R. Y. L.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Research Article

Nucleoplasmic mobilization of nucleostemin stabilizes MDM2 and promotes G2-M progression and cell survival

Lingjun Meng, Tao Lin and Robert Y. L. Tsai*

Center for Cancer and Stem Cell Biology, Alkek Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX 77030, USA

* Author for correspondence (e-mail: rtsai{at}ibt.tamhsc.edu)

Accepted 5 September 2008

Nucleolar disassembly occurs during mitosis and nucleolar stress, releasing several MDM2-interactive proteins residing in the nucleolus that share the common activity of p53 stabilization. Here, we demonstrate that mobilization of nucleostemin, a nucleolar protein enriched in cancer and stem cells, has the opposite role of stabilizing MDM2 and suppressing p53 functions. Our results show that nucleostemin increases the protein stability and nucleoplasmic retention of MDM2, and competes with L23 for MDM2 binding. These activities were significantly elevated when nucleostemin is released into the nucleoplasm by mutations that abolish its nucleolar localization or by chemotherapeutic agents that disassemble the nucleoli. Nucleostemin depletion decreases MDM2 protein, increases transcription activity without affecting the level of p53 protein, and triggers G2-M arrest and cell death in U2OS cells but not in H1299 cells. This work reveals that nucleoplasmic relocation of nucleostemin during nucleolar disassembly safeguards the G2-M transit and survival of continuously dividing cells by MDM2 stabilization and p53 inhibition.

Key words: Nucleostemin, MDM2, Cancer, Ubiquitylation, p53


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
L. Romanova, S. Kellner, N. Katoku-Kikyo, and N. Kikyo
Novel Role of Nucleostemin in the Maintenance of Nucleolar Architecture and Integrity of Small Nucleolar Ribonucleoproteins and the Telomerase Complex
J. Biol. Chem., September 25, 2009; 284(39): 26685 - 26694.
[Abstract] [Full Text] [PDF]

Home page
 JCBHome page
T. Pederson and R. Y.L. Tsai
In search of nonribosomal nucleolar protein function and regulation
J. Cell Biol., March 23, 2009; 184(6): 771 - 776.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2008