The role of MCAF1 in normal and cancer cell proliferation

• Main Authors: Ke-MiTuan, 段可咪
• Other Authors: Ding-Yen Lin
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/44983016266422157532

碩士 === 國立成功大學 === 生物資訊與訊息傳遞研究所 === 101 === MBD1-containing chromatin-associated factor 1 (MCAF1), also known as ATFa-associated modulator (AM) and activating transcription factor 7-interacting protein (ATF7IP), is involved in methylated DNA-binding domain protein 1 (MBD1)-dependent transcriptional repression via heterochromatin assembly. MCAF1 can bind the transcriptional repression domain of MBD1 and further recruit SET domain bifurcated 1 (SETDB1) for gene silencing in methylated DNA regions. Additionally, elevated expressions of MCAF1 have been observed in several human cancers. Currently, the mechanisms underlying the MCAF1- regulated cell proliferation are not fully understood. In this study, we established HeLa, NIH3T3 cell lines and human diploid fibroblasts (IMR-90) that exhibited stable expression of ectopic MCAF1. Interestingly, ectopic expression of MCAF1 causes HeLa cells to growth arrest through the induction of p21. Specifically, stable overexpression of MCAF1 into NIH3T3 and IMR90 cells induces cellular senescence. Microarray analysis indicates several genes potentially involved in MCAF1-mediated control of cell proliferation. Notably, the results of analyzing expression levels of MCAF1 between tumors and matched normal tissues showed significant changes (both up- and down-regulation) in its expression in different types of cancer. Because of the functional role of MCAF1 in regulating cell proliferation and transcription, the current investigation, in accordance with previous studies, suggests additional levels of regulation of MCAF1 functions in cancer progression in cell and tissue context-dependent manners.