Abstract

Abstract Our long term research goal is to understand the biochemical mechanism of immortalization of human epithelial cells that represents early step in cancer progression. Over the years, we have generated several epithelial cell immortalization models, using viral oncogenes, mutated cancer genes, as well as radiation treatment of cells. In one of such immortalization model, we identified alteration/deficiency in activation (ADA3) protein as a novel human papilloma virus E6 oncoprotein binding protein, and as a regulator of p53 function. We and others have shown that human ADA3 protein is an essential component of various Histone acetyl transferase complexes (HATs) and thus controls transactivation of various transcriptional factors. To gain insight into the physiological importance of ADA3, we established a conditional knockout mouse model and showed that loss of ADA3 led to embryonic lethality at an early stage of development. Using ADA3lox/lox mouse embryonic fibroblast (MEF) cell lines, we further showed that ADA3 plays an important role in DNA damage and repair pathway. Adenovirus cre-mediated deletion of ADA3 led to a global reduction of histone acetylation, severe G2/M cell cycle arrest, various aberration in nuclear structures, and massive chromosome aberration. Significantly, cells lacking ADA3 showed defects in recruitment of DNA repair associated proteins, BRCA1 and 53BP1 to the DNA damage foci. These results implicate ADA3 as a major cell cycle and DNA repair response regulating protein. These findings in the context of oncogenesis and chemotherapy will be discussed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3929. doi:10.1158/1538-7445.AM2011-3929

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.