Evasion of the P53 Tumour Surveillance Network by Tumour-derived MYC Mutants

Overview

Journal Nature

Specialty Science

Date 2005 Aug 12

PMID 16094360

Citations 230

Authors

Michael T Hemann

Anka Bric

Julie Teruya-Feldstein

Andreas Herbst

Jonas A Nilsson

Carlos Cordon-Cardo

John L Cleveland

William P Tansey

Scott W Lowe

Affiliations

Soon will be listed here.

Abstract

The c-Myc oncoprotein promotes proliferation and apoptosis, such that mutations that disable apoptotic programmes often cooperate with MYC during tumorigenesis. Here we report that two common mutant MYC alleles derived from human Burkitt's lymphoma uncouple proliferation from apoptosis and, as a result, are more effective than wild-type MYC at promoting B cell lymphomagenesis in mice. Mutant MYC proteins retain their ability to stimulate proliferation and activate p53, but are defective at promoting apoptosis due to a failure to induce the BH3-only protein Bim (a member of the B cell lymphoma 2 (Bcl2) family) and effectively inhibit Bcl2. Disruption of apoptosis through enforced expression of Bcl2, or loss of either Bim or p53 function, enables wild-type MYC to produce lymphomas as efficiently as mutant MYC. These data show how parallel apoptotic pathways act together to suppress MYC-induced transformation, and how mutant MYC proteins, by selectively disabling a p53-independent pathway, enable tumour cells to evade p53 action during lymphomagenesis.

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