Identification of a novel nucleophosmin‐interaction motif in the tumor suppressor p14arf

Identification of a novel nucleophosmin‐interaction motif in the tumor suppressor p14arf The tumor suppressor p14arf interacts, in response to oncogenic signals, with the p53 E3‐ubiquitin ligase HDM2, thereby resulting in p53 stabilization and activation. In addition, it also exerts tumor‐suppressive functions in p53‐independent contexts. The activities of p14arf are regulated by the nucleolar chaperone nucleophosmin (NPM1), which controls its levels and cellular localization. In acute myeloid leukemia with mutations in the NPM1 gene, mutated NPM1 aberrantly translocates in the cytosol carrying with itself p14arf that is subsequently degraded, thus impairing the p14arf‐HDM2‐p53 axis. In this work we investigated the complex between these two proteins by means of NMR and other techniques. We identified a novel NPM1‐interacting motif in the C‐terminal region of p14arf, which corresponds to its predicted nucleolar localization signal. This motif recognizes a specific region of the NPM1 N‐terminal domain and, upon binding, the two proteins form soluble high molecular weight complexes. By NMR, we identified critical residues on both proteins involved in the interaction. Collectively, our data provide a structural framework to rationalize the overall assembly of the p14arf‐NPM1 supramolecular complexes. A number of p14arf cancer‐associated mutations cluster in this motif and their effect on the interaction with NPM1 was also analyzed. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Febs Journal Wiley

Identification of a novel nucleophosmin‐interaction motif in the tumor suppressor p14arf

Loading next page...
 
/lp/wiley/identification-of-a-novel-nucleophosmin-interaction-motif-in-the-tumor-sPq9BUj0SV
Publisher
Wiley Subscription Services, Inc., A Wiley Company
Copyright
Copyright © 2018 Federation of European Biochemical Societies
ISSN
1742-464X
eISSN
1742-4658
D.O.I.
10.1111/febs.14373
Publisher site
See Article on Publisher Site

Abstract

The tumor suppressor p14arf interacts, in response to oncogenic signals, with the p53 E3‐ubiquitin ligase HDM2, thereby resulting in p53 stabilization and activation. In addition, it also exerts tumor‐suppressive functions in p53‐independent contexts. The activities of p14arf are regulated by the nucleolar chaperone nucleophosmin (NPM1), which controls its levels and cellular localization. In acute myeloid leukemia with mutations in the NPM1 gene, mutated NPM1 aberrantly translocates in the cytosol carrying with itself p14arf that is subsequently degraded, thus impairing the p14arf‐HDM2‐p53 axis. In this work we investigated the complex between these two proteins by means of NMR and other techniques. We identified a novel NPM1‐interacting motif in the C‐terminal region of p14arf, which corresponds to its predicted nucleolar localization signal. This motif recognizes a specific region of the NPM1 N‐terminal domain and, upon binding, the two proteins form soluble high molecular weight complexes. By NMR, we identified critical residues on both proteins involved in the interaction. Collectively, our data provide a structural framework to rationalize the overall assembly of the p14arf‐NPM1 supramolecular complexes. A number of p14arf cancer‐associated mutations cluster in this motif and their effect on the interaction with NPM1 was also analyzed.

Journal

Febs JournalWiley

Published: Jan 1, 2018

Keywords: ; ; ; ; ;

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 12 million articles from more than
10,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Unlimited reading

Read as many articles as you need. Full articles with original layout, charts and figures. Read online, from anywhere.

Stay up to date

Keep up with your field with Personalized Recommendations and Follow Journals to get automatic updates.

Organize your research

It’s easy to organize your research with our built-in tools.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

Monthly Plan

  • Read unlimited articles
  • Personalized recommendations
  • No expiration
  • Print 20 pages per month
  • 20% off on PDF purchases
  • Organize your research
  • Get updates on your journals and topic searches

$49/month

Start Free Trial

14-day Free Trial

Best Deal — 39% off

Annual Plan

  • All the features of the Professional Plan, but for 39% off!
  • Billed annually
  • No expiration
  • For the normal price of 10 articles elsewhere, you get one full year of unlimited access to articles.

$588

$360/year

billed annually
Start Free Trial

14-day Free Trial