p53-independent functions of the p19(ARF) tumor suppressor

The p19(ARF) tumor suppressor antagonizes Mdm2 to induce p53-dependent cell cycle arrest. Individual TKO (triple knock out) mice nullizygous for ARF, p53, and Mdm2 develop multiple tumors at a frequency greater than those observed in animals lacking both p53 and Mdm2 or p53 alone, demonstrating that...

Full description

Saved in:
Bibliographic Details
Published in:Genes & development 2000-09, Vol.14 (18), p.2358-2365
Main Authors: Weber, J D, Jeffers, J R, Rehg, J E, Randle, D H, Lozano, G, Roussel, M F, Sherr, C J, Zambetti, G P
Format: Article
Language:English
Subjects:
Animals
Cells, Cultured
Fluorescent Antibody Technique
Genes, Tumor Suppressor
Immunoblotting
Mice
Mice, Inbred C57BL
Mice, Knockout
Neoplasms - genetics
Neoplasms - pathology
Nuclear Proteins
Polymerase Chain Reaction
Proteins - genetics
Proteins - metabolism
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - physiology
Proto-Oncogene Proteins c-mdm2
Tumor Suppressor Protein p14ARF
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - physiology
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The p19(ARF) tumor suppressor antagonizes Mdm2 to induce p53-dependent cell cycle arrest. Individual TKO (triple knock out) mice nullizygous for ARF, p53, and Mdm2 develop multiple tumors at a frequency greater than those observed in animals lacking both p53 and Mdm2 or p53 alone, demonstrating that p19(ARF) can act independently of the Mdm2-p53 axis in tumor surveillance. Reintroduction of ARF into TKO mouse embryo fibroblasts (MEFs), but not into those lacking both p53 and ARF, arrested the cell division cycle in the G1 phase. Inhibition of the retinoblastoma protein had no effect on the ability of ARF to arrest TKO MEFs. Thus, in the absence of Mdm2, p19(ARF) interacts with other targets to inhibit cell proliferation.
ISSN:0890-9369
DOI:10.1101/gad.827300