Cloning of the rat Waf1/Cip1 gene
The progression of eukaryotic cells through the cell cycle involves the sequential expression of specific genes. This process is regulated by both external and internal stimuli that prevent the cell from prematurely entering the next phase before all macromolecular events have been completed. The activation and subsequent inactivation of cyclin dependent kinases (Cdks) represent one internal stimuli required to regulate the transit of cells from one stage of the cell cycle to the next. Another member of this regulatory cascade is the p53 tumor suppressor gene, which controls a G{sub 1} checkpoint at which the cell cycle can be arrested prior to the initiation of DNA synthesis. Following DNA damage, p53 protein levels rise, and entry into S phase is delayed, presumably to allow time for repair of the lesions. When p53 function is lost, cells containing damaged DNA template enter S phase leading to fixation and propagation of genetic alterations. Recently, evidence linking the growth-suppressing activity of p53 and inactivation of Cdks has been provided by the cloning of the Waf1/Cip1 gene. Waf1/Cip1 encodes a protein of M{sub r} 21,000 (p21), which inhibits Cdks in vitro. The overexpression of Waf1/Cip1 in cells inhibits cell growth, suggesting that p21 is a downstream mediator of p53 function. Loss of Waf1/Cip1 gene function could lead to deregulation of the cell cycle and contribute to the development of the neoplastic phenotype in tumors that do not contain mutations in the p53 gene. The purpose of the present investigation was to clone the rat Waf1/Cip1 gene,then determine the frequency for alteration of this gene in lung tumors induced by X-rays.
- Research Organization:
- Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM (United States). Inhalation Toxicology Research Inst.
- DOE Contract Number:
- AC04-76EV01013
- OSTI ID:
- 54821
- Report Number(s):
- ITRI-144; ON: DE95007526; TRN: 95:012762
- Resource Relation:
- Other Information: PBD: Nov 1994; Related Information: Is Part Of Inhalation Toxicology Research Institute annual report, October 1, 1993--September 30, 1994; Belinsky, S.A.; Hoover, M.D.; Bradley, P.L. [eds.]; PB: 211 p.
- Country of Publication:
- United States
- Language:
- English
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