Stability of nucleolar versus non-nucleolar forms of human p14ARF

Fusion proteins containing the amino-terminal domain of human p14 ARF linked to green fluorescent protein are able to bind MDM2 and stabilize p53 without localization in the nucleolus. However, these fusion proteins are inherently unstable, with half-lives considerably shorter than either authentic...

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Veröffentlicht in:Oncogene 2004-08, Vol.23 (37), p.6186-6192
Hauptverfasser: Rodway, Helen, Llanos, Susana, Rowe, Janice, Peters, Gordon
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container_end_page 6192
container_issue 37
container_start_page 6186
container_title Oncogene
container_volume 23
creator Rodway, Helen
Llanos, Susana
Rowe, Janice
Peters, Gordon
description Fusion proteins containing the amino-terminal domain of human p14 ARF linked to green fluorescent protein are able to bind MDM2 and stabilize p53 without localization in the nucleolus. However, these fusion proteins are inherently unstable, with half-lives considerably shorter than either authentic ARF or chimaeras containing the entire coding domain, both of which are predominantly nucleolar. We present evidence that the unstable fusion proteins are significantly stabilized if redirected to the nucleolus by addition of a basic motif based on the nuclear localization signal of SV40 T-antigen. Moreover, the stability of these proteins can be enhanced by modulating the functions of MDM2 and p53. These data are consistent with a model in which ARF interacts with MDM2 in the nucleoplasm but is consequently subject to proteasomal degradation. Nucleolar localization may serve to store or stabilize ARF.
doi_str_mv 10.1038/sj.onc.1207854
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source Nature Journals Online; SpringerLink (Online service); EZB Electronic Journals Library
subjects Antigens
Apoptosis
Biological and medical sciences
Cell Biology
Cell physiology
Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
Fundamental and applied biological sciences. Psychology
Green fluorescent protein
Human Genetics
Internal Medicine
Localization
MDM2 protein
Medicine
Medicine & Public Health
Molecular and cellular biology
Nucleoli
Oncology
original-paper
p53 Protein
Proteasomes
Proteins
title Stability of nucleolar versus non-nucleolar forms of human p14ARF
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