Impeded Nedd4-1-Mediated Ras Degradation Underlies Ras-Driven Tumorigenesis

Zeng, T and Wang, Q and Fu, J and Lin, Q and Bi, J and Ding, W and Qiao, Y and Zhang, S and Zhao, W and Lin, H and Wang, M and Lu, B and Deng, X and Zhou, D and Yin, Z and Wang, HR (2014) Impeded Nedd4-1-Mediated Ras Degradation Underlies Ras-Driven Tumorigenesis. Cell Reports, 7 (3). 871 - 882.

Preview	PDF Published Version Available under License : See the attached license file. Download (4MB)
	Plain Text (licence) Available under License : See the attached license file. Download (1kB)

Abstract

RAS genes are among the most frequently mutated proto-oncogenes in cancer. However, how Ras stability is regulated remains largely unknown. Here, we report a regulatory loop involving the E3 ligase Nedd4-1, Ras, and PTEN. We found that Ras signaling stimulates the expression of Nedd4-1, which in turn acts as an E3 ubiquitin ligase that regulates Ras levels. Importantly, Ras activation, either by oncogenic mutations or by epidermal growth factor (EGF) signaling, prevents Nedd4-1-mediated Ras ubiquitination. This leads to Ras-induced Nedd4-1 overexpression, and subsequent degradation of the tumor suppressor PTEN in both human cancer samples and cancer cells. Our study thus unravels the molecular mechanisms underlying the interplay of Ras, Nedd4-1, and PTEN and suggests a basis for the high prevalence of Ras-activating mutations and EGF hypersignaling in cancer. © 2014 The Authors.

---

Share

Citation/Export:	Select format... Citation - Text Citation - HTML Endnote BibTex Dublin Core OpenURL MARC (ISO 2709) METS MODS EP3 XML Reference Manager Refer
Social Networking:	Share |

---

Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Zeng, T Wang, Q Fu, J Lin, Q Bi, J Ding, W Qiao, Y Zhang, S Zhao, W Lin, H Wang, M Lu, B binfeng@pitt.edu BINFENG Deng, X Zhou, D Yin, Z Wang, HR
Date:	1 January 2014
Date Type:	Publication
Journal or Publication Title:	Cell Reports
Volume:	7
Number:	3
Page Range:	871 - 882
DOI or Unique Handle:	10.1016/j.celrep.2014.03.045
Schools and Programs:	School of Medicine > Immunology
Refereed:	Yes
Date Deposited:	22 May 2015 21:51
Last Modified:	02 Feb 2019 16:58
URI:	http://d-scholarship.pitt.edu/id/eprint/24723

---

Metrics

Monthly Views for the past 3 years

Plum Analytics

Altmetric.com

---

Actions (login required)

View Item