Mitochondrially targeted wild-type p53 suppresses growth of mutant p53 lymphomas in vivo
- 8 May 2006
- journal article
- Published by Springer Nature in Oncogene
- Vol. 25 (45), 6133-6139
- https://doi.org/10.1038/sj.onc.1209641
Abstract
The complex apoptotic functions of the p53 tumor suppressor are central to its antineoplastic activity in vivo. Besides its well-known action as a transcriptional activator of apoptotic genes, p53 exerts a direct proapoptotic role at the mitochondria via protein–protein interactions with Bcl2 family members, thus executing the shortest known circuitry of p53 death signaling. We recently reported that exclusive delivery of p53 to mitochondria exerts a significant in vivo tumor suppressor activity in p53-null lymphomas. However, it was unknown whether mitochondrially targeted p53 has suppressor activities in tumors harboring missense mutants, which constitute the vast majority of p53 alterations in human tumors. Here, we show that targeting p53 to mitochondria does confer a significant growth disadvantage in B-lymphomas expressing various point mutants of p53, resulting in efficient apoptosis induction in vitro and in vivo in mice.Keywords
This publication has 29 references indexed in Scilit:
- Adenovirus-Mediated p53 Treatment Enhances Photodynamic Antitumor ResponseHuman Gene Therapy, 2006
- Epigenetic gene silencing in cancer – a mechanism for early oncogenic pathway addiction?Nature Reviews Cancer, 2006
- Irradiation-induced Translocation of p53 to Mitochondria in the Absence of ApoptosisPublished by Elsevier ,2005
- Mitochondrially Targeted p53 Has Tumor Suppressor Activities In vivoCancer Research, 2005
- Viral and cellular oncogenes induce rapid mitochondrial translocation of p53 in primary epithelial and endothelial cells early in apoptosisFEBS Letters, 2005
- Stress-induced p53 runs a transcription-independent death programBiochemical and Biophysical Research Communications, 2005
- Direct Activation of Bax by p53 Mediates Mitochondrial Membrane Permeabilization and ApoptosisScience, 2004
- The codon 72 polymorphic variants of p53 have markedly different apoptotic potentialNature Genetics, 2003
- The IARC TP53 database: New online mutation analysis and recommendations to usersHuman Mutation, 2002
- Hypoxia death stimulus induces translocation of p53 protein to mitochondriaFEBS Letters, 2001