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PMID: 9789064 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

p19(Arf) induces p53-dependent apoptosis during abelson virus-mediated pre-B cell transformation.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 22 ·1998-10-27 ·Pages 13194-9

Radfar A, Unnikrishnan I, Lee HW, DePinho RA, Rosenberg N

Abstract

The Ink4a/Arf locus encodes p16(Ink4a) and p19(Arf) and is among the most frequently mutated tumor suppressor loci in human cancer. In mice, many of these effects appear to be mediated by interactions between p19(Arf) and the p53 tumor-suppressor protein. Because Tp53 mutations are a common feature of the multistep pre-B cell transformation process mediated by Abelson murine leukemia virus (Ab-MLV), we examined the possibility that proteins encoded by the Ink4a/Arf locus also play a role in Abelson virus transformation. Analyses of primary transformants revealed that both p16(Ink4a) and p19(Arf) are expressed in many of the cells as they emerge from the apoptotic crisis that characterizes the transformation process. Analyses of primary transformants from Ink4a/Arf null mice revealed that these cells bypassed crisis. Because expression of p19(Arf) but not p16 (Ink4a) induced apoptosis in Ab-MLV-transformed pre-B cells, p19(Arf) appears to be responsible for these events. Consistent with the link between p19(Arf) and p53, Ink4a/Arf expression correlates with or precedes the emergence of cells expressing mutant p53. These data demonstrate that p19(Arf) is an important part of the cellular defense mounted against transforming signals from the Abl oncoprotein and provide direct evidence that the p19(Arf)-p53 regulatory loop plays an important role in lymphoma induction.

MeSH Terms
3T3 Cells Abelson murine leukemia virus/genetics Animals Apoptosis B-Lymphocytes Cell Line, Transformed Cell Transformation, Neoplastic Cyclin-Dependent Kinase Inhibitor p16/physiology Genes, p16 Genes, p53 Humans Mice Proteins/genetics,physiology Recombinant Proteins/metabolism Transfection Tumor Suppressor Protein p14ARF Tumor Suppressor Protein p53/physiology
Chemicals
Cyclin-Dependent Kinase Inhibitor p16 Proteins Recombinant Proteins Tumor Suppressor Protein p14ARF Tumor Suppressor Protein p53
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Radfar A
The Immunology Program, Tufts University School of Medicine, Boston, MA 02111, USA.
Unnikrishnan I
Lee H W
DePinho R A
Rosenberg N
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.95.22.13194
Published
1998-10-27
Pages
13194-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC23757
Subset
IM
Grants
NCI NIH HHS · R01 CA033771 · United States
NCI NIH HHS · CA 33771 · United States
NEI NIH HHS · EY 11267 · United States
External Links
PubMed source DOI: 10.1073/pnas.95.22.13194 PMC Full Text View journal details
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