A DNA damage and stress inducible G protein-coupled receptor blocks cells in G2/M
- Zhigang Weng*†,
- Anne-Catherine Fluckiger*‡,
- Sazuku Nisitani§,
- Matthew I. Wahl*,
- Lu Q. Le¶,
- Charity A. Hunter*,
- Anthony A. Fernal‖,
- Michelle M. Le Beau‖, and
- Owen N. Witte*§**
- *Department of Microbiology, Immunology and Molecular Genetics, §Howard Hughes Medical Institute, ¶Medical Scientist Training Program, University of California, Los Angeles, CA 90095; and ‖Department of Medicine, Section of Hematology/Oncology, University of Chicago, Chicago, IL 60637
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Contributed by Owen N. Witte
Abstract
Cell cycle progression is monitored by highly coordinated checkpoint machinery, which is activated to induce cell cycle arrest until defects like DNA damage are corrected. We have isolated an anti-proliferative cell cycle regulator named G2A (for G2 accumulation), which is predominantly expressed in immature T and B lymphocyte progenitors and is a member of the seven membrane-spanning G protein-coupled receptor family. G2A overexpression attenuates the transformation potential of BCR-ABL and other oncogenes, and leads to accumulation of cells at G2/M independently of p53 and c-Abl. G2A can be induced in lymphocytes and to a lesser extent in nonlymphocyte cell lines or tissues by multiple stimuli including different classes of DNA-damaging agents and serves as a response to damage and cellular stimulation which functions to slow cell cycle progression.
Footnotes
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↵† Present address: ARIAD Pharmaceuticals Inc., 26 Landsdowne Street, Cambridge, MA 02139.
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↵‡ Present address: PharMingen, 10975 Torreyana Road, San Diego, CA 92121.
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↵** To whom reprint requests should be addressed. e-mail: owenw{at}microbio.ucla.edu.
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Data deposition: The sequence reported in this paper has been deposited in the GenBank database (accession no. AF083442).
ABBREVIATIONS
- GFP,
- green fluorescence protein;
- ALLN,
- N-acetyl-l-leucinyl-l-leucinyl-l-norleucinal;
- RDA,
- representational difference analysis;
- GPCR,
- G protein-coupled receptor;
- RT-PCR,
- reverse transcription–PCR;
- wt,
- wild type;
- FACS,
- fluorescence-activated cell sorter;
- SH2,
- Src homology 2
- Accepted August 18, 1998.
- Copyright © 1998, The National Academy of Sciences
