Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest

Dawn E Quelle; Frédérique Zindy; Richard A Ashmun; Charles J Sherr

doi:10.1016/0092-8674(95)90214-7

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Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest

Journal article

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Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest

Dawn E Quelle, Frédérique Zindy, Richard A Ashmun and Charles J Sherr

Cell (Cambridge), Vol.83(6), pp.993-1000

1995

DOI: 10.1016/0092-8674(95)90214-7

PMID: 8521522

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Abstract

The INK4a (MTS1, CDKN2) gene encodes an inhibitor (p16 INK4a) of the cyclin D-dependent kinases CDK4 and CDK6 that blocks them from phosphorylating the retinoblastoma protein (pRB) and prevents exit from the G1 phase of the cell cycle. Deletions and mutations involving INK4a occur frequently in cancers, implying that p16 INK4a, like pRB, suppresses tumor formation. An unrelated protein (p19 ARF) arises in major part from an alternative reading frame of the mouse INK4a gene, and its ectopic expression in the nucleus of rodent fibroblasts induces G1 and G2 phase arrest. Economical reutilization of coding sequences in this manner is practically without precedent in mammalian genomes, and the unitary inheritance of p16 INK4a and p19 ARF may underlie their dual requirement in cell cycle control.

Details

Title: Subtitle: Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest
Creators: Dawn E Quelle - Howard Hughes Medical Institute St. Jude Children's Research Hospital 332 North Lauderdale Memphis, Tennessee 38101, USA
Frédérique Zindy - Department of Tumor Cell Biology St. Jude Children's Research Hospital 332 North Lauderdale Memphis, Tennessee 38101, USA
Richard A Ashmun - Department of Tumor Cell Biology St. Jude Children's Research Hospital 332 North Lauderdale Memphis, Tennessee 38101, USA
Charles J Sherr - Howard Hughes Medical Institute St. Jude Children's Research Hospital 332 North Lauderdale Memphis, Tennessee 38101, USA
Resource Type: Journal article
Publication Details: Cell (Cambridge), Vol.83(6), pp.993-1000
Publisher: Elsevier Inc
DOI: 10.1016/0092-8674(95)90214-7
PMID: 8521522
ISSN: 0092-8674
eISSN: 1097-4172
Language: English
Date published: 1995
Academic Unit: Pathology; Neuroscience and Pharmacology
Record Identifier: 9984040549702771

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