This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vieyra, D. Articles by Riabowol, K. Search for Related Content PubMed PubMed Citation Articles by Vieyra, D. Articles by Riabowol, K.

ING1 Isoforms Differentially Affect Apoptosis in a Cell Age-dependent Manner¹

Cancer Biology Research Group, Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, T2N 4N1 Canada [D. V., Y. H., D. B., R. J., K. R.]; Department of Surgery II, Nagoya City University Medical School, Nagoya 467-8601, Japan [T. T., Y. H.]; Southern Alberta Cancer Research Centre Hybridoma Facility, Calgary, Alberta, T2N 4N1 Canada [D. B., K. R.]; and Genome Prairie Consortium, Calgary, Alberta, T2N 1N4 Canada [R. J.]

Recently, several novel human ING1 isoforms have been cloned. However,the biochemical functions and the involvement of these proteins in apoptosis remain uncharacterized. We have examined the apoptotic effects and biochemical functions of the two major human ING1 isoforms p47^ING1a and p33^ING1b in young and senescent human diploid fibroblasts induced to enter into apoptosis by diverse treatments. We have found that ING1 displayed isoform-, stimulus- and cell age-dependent apoptotic properties. We present evidence indicating that ING1 proteins bind to chromatin and are regulated in a manner related to their apoptotic properties. In agreement with previous reports, we have found that only young but not senescent fibroblasts were able to enter into apoptosis induced by growth factor deprivation. This effect was accompanied by up-regulation of endogenous p33^ING1b. Ectopic up-regulation of p33^ING1b, but not p47^ING1a, also induced apoptosis and sensitized young but not senescent cells to UV irradiation and hydrogen peroxide-mediated apoptosis. Cotransfection of p33^ING1b and the tumor suppressor p53 increased the percentage of apoptotic cells yielded by either of these two proteins alone, in agreement with data from tumor cell models. Finally, we found that the chromatin binding affinity of p33^ING1b was increased in senescent cells, which were resistant to apoptosis. Together, these data support the idea that the apoptotic functions of ING1 may be exerted by chromatin-related functions that are subject to cell age-dependent mechanisms of regulation.

This article has been cited by other articles:

				J. Luo, S. Shah, K. Riabowol, and P. E. Mains The Caenorhabditis elegans ing-3 Gene Regulates Ionizing Radiation-Induced Germ-Cell Apoptosis in a p53-Associated Pathway Genetics, February 1, 2009; 181(2): 473 - 482. [Abstract] [Full Text] [PDF]

				X. Feng, S. Bonni, and K. Riabowol HSP70 Induction by ING Proteins Sensitizes Cells to Tumor Necrosis Factor Alpha Receptor-Mediated Apoptosis Mol. Cell. Biol., December 15, 2006; 26(24): 9244 - 9255. [Abstract] [Full Text] [PDF]

				W. Gong, M. Russell, K. Suzuki, and K. Riabowol Subcellular Targeting of p33ING1b by Phosphorylation-Dependent 14-3-3 Binding Regulates p21WAF1 Expression Mol. Cell. Biol., April 15, 2006; 26(8): 2947 - 2954. [Abstract] [Full Text] [PDF]

				D.-H. Shen, K. Y.-K. Chan, U.-S. Khoo, H. Y.-S. Ngan, W.-C. Xue, P.-M. Chiu, P. Ip, and A. N.-Y. Cheung Epigenetic and genetic alterations of p33ING1b in ovarian cancer Carcinogenesis, April 1, 2005; 26(4): 855 - 863. [Abstract] [Full Text] [PDF]

				D. Vieyra, D. L. Senger, T. Toyam, H. Muzik, P. M. A. Brasher, R. N. Johnston, K. Riabowol, and P. A. Forsyth Altered Subcellular Localization and Low Frequency of Mutations of ING1 in Human Brain Tumors Clin. Cancer Res., December 1, 2003; 9(16): 5952 - 5961. [Abstract] [Full Text] [PDF]

				H. Kataoka, P. Bonnefin, D. Vieyra, X. Feng, Y. Hara, Y. Miura, T. Joh, H. Nakabayashi, H. Vaziri, C. C. Harris, et al. ING1 Represses Transcription by Direct DNA Binding and through Effects on p53 Cancer Res., September 15, 2003; 63(18): 5785 - 5792. [Abstract] [Full Text] [PDF]