Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARF

T Kamijo; F Zindy; M F Roussel; D E Quelle; J R Downing; R A Ashmun; G Grosveld; C J Sherr

doi:10.1016/s0092-8674(00)80452-3

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Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARF

Journal article

Open access

Peer reviewed

Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARF

T Kamijo, F Zindy, M F Roussel, D E Quelle, J R Downing, R A Ashmun, G Grosveld and C J Sherr

Cell (Cambridge), Vol.91(5), pp.649-659

11/28/1997

DOI: 10.1016/s0092-8674(00)80452-3

PMID: 9393858

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Abstract

The INK4a tumor suppressor locus encodes p16INK4a, an inhibitor of cyclin D-dependent kinases, and p19ARF, an alternative reading frame protein that also blocks cell proliferation. Surprisingly, mice lacking p19ARF but expressing functional p16INK4a develop tumors early in life. Their embryo fibroblasts (MEFs) do not senesce and are transformed by oncogenic Ha-ras alone. Conversion of ARF+/+ or ARF+/- MEF strains to continuously proliferating cell lines involves loss of either p19ARF or p53. p53-mediated checkpoint control is unperturbed in ARF-null fibroblast strains, whereas p53-negative cell lines are resistant to p19ARF-induced growth arrest. Therefore, INK4a encodes growth inhibitory proteins that act upstream of the retinoblastoma protein and p53. Mutations and deletions targeting this locus in cancer cells are unlikely to be functionally equivalent.

Phenotype

Cell Division - genetics

Humans

Mice, Inbred C57BL

Cyclin-Dependent Kinase Inhibitor p16 - genetics

Exons - genetics

Male

Kidney - cytology

G1 Phase - physiology

Open Reading Frames - genetics

Proteins - genetics

Tumor Suppressor Protein p53 - physiology

Animals

Mice, Mutant Strains

Gene Deletion

Neoplasms, Experimental - genetics

Female

Mice

Mutagenesis - physiology

Leukemia, Erythroblastic, Acute

Tumor Suppressor Protein p14ARF

Gene Expression Regulation, Neoplastic - physiology

3T3 Cells

Details

Title: Subtitle: Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARF
Creators: T Kamijo - Howard Hughes Medical Institute, Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA
F Zindy
M F Roussel
D E Quelle
J R Downing
R A Ashmun
G Grosveld
C J Sherr
Resource Type: Journal article
Publication Details: Cell (Cambridge), Vol.91(5), pp.649-659
DOI: 10.1016/s0092-8674(00)80452-3
PMID: 9393858
NLM abbreviation: Cell
ISSN: 0092-8674
eISSN: 1097-4172
Publisher: United States
Grant note: CA71907 / NCI NIH HHS CA21765 / NCI NIH HHS
Language: English
Date published: 11/28/1997
Academic Unit: Pathology; Neuroscience and Pharmacology
Record Identifier: 9984040442702771

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