The RASSF1A tumor suppressor
Author:
Donninger Howard1, Vos Michele D.2, Clark Geoffrey J.1
Affiliation:
1. Molecular Targets Group, Department of Medicine, J. G. Brown Cancer Center, University of Louisville, 119C Baxter Boulevard, 580 S. Preston Street, Louisville, KY 40202, USA 2. Research Analysis and Evaluation Branch, NCI, Rockville, MD, USA
Abstract
RASSF1A (Ras association domain family 1 isoform A) is a recently discovered tumor suppressor whose inactivation is implicated in the development of many human cancers. Although it can be inactivated by gene deletion or point mutations, the most common contributor to loss or reduction of RASSF1A function is transcriptional silencing of the gene by inappropriate promoter methylation. This epigenetic mechanism can inactivate numerous tumor suppressors and is now recognized as a major contributor to the development of cancer.RASSF1A lacks apparent enzymatic activity but contains a Ras association (RA) domain and is potentially an effector of the Ras oncoprotein. RASSF1A modulates multiple apoptotic and cell cycle checkpoint pathways. Current evidence supports the hypothesis that it serves as a scaffold for the assembly of multiple tumor suppressor complexes and may relay pro-apoptotic signaling by K-Ras.
Publisher
The Company of Biologists
Reference134 articles.
1. Agathanggelou, A., Honorio, S., Macartney, D. P., Martinez, A., Dallol, A., Rader, J., Fullwood, P., Chauhan, A., Walker, R., Shaw, J. A. et al. (2001). Methylation associated inactivation of RASSF1A from region 3p21.3 in lung, breast and ovarian tumors. Oncogene20, 1509-1518. 2. Agathanggelou, A., Bièche, I., Ahmed-Choudhury, J., Nicke, B., Dammann, R., Baksh, S., Gao, B., Minna, J. D., Downward, J., Maher, E. R. et al. (2003). Identification of novel gene expression targets for the Ras association domain family 1 (RASSF1A) tumor suppressor gene in non-small cell lung cancer and neuroblastoma. Cancer Res.63, 5344-5351. 3. Agathanggelou, A., Cooper, W. N. and Latif, F. (2005). Role of the Ras-association domain family 1 tumor suppressor gene in human cancers. Cancer Res.65, 3497-3508. 4. Ahmed-Choudhury, J., Agathanggelou, A., Fenton, S. L., Ricketts, C., Clark, G. J., Maher, E. R. and Latif, F. (2005). Transcriptional regulation of cyclin A2 by RASSF1A through the enhanced binding of p120E4F to the cyclin A2 promoter. Cancer Res.65, 2690-2697. 5. Akino, K., Toyota, M., Suzuki, H., Mita, H., Sasaki, Y., Ohe-Toyota, M., Issa, J. P., Hinoda, Y., Imai, K. and Tokino, T. (2005). The Ras effector RASSF2 is a novel tumor-suppressor gene in human colorectal cancer. Gastroenterology129, 156-169.
Cited by
353 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|