Donninger Howard, Vos Michele D, Clark Geoffrey J
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.
J Cell Sci. 2007 Sep 15;120(Pt 18):3163-72. doi: 10.1242/jcs.010389.
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.
RASSF1A（Ras关联结构域家族1亚型A）是一种最近发现的肿瘤抑制因子，其失活与多种人类癌症的发生发展有关。尽管它可通过基因缺失或点突变而失活，但导致RASSF1A功能丧失或降低的最常见原因是该基因因不适当的启动子甲基化而发生转录沉默。这种表观遗传机制可使众多肿瘤抑制因子失活，目前被认为是癌症发生发展的主要因素。RASSF1A缺乏明显的酶活性，但含有一个Ras关联（RA）结构域，可能是Ras癌蛋白的效应器。RASSF1A可调节多种凋亡和细胞周期检查点途径。目前的证据支持这样一种假说，即它作为多种肿瘤抑制复合物组装的支架，可能通过K-Ras传递促凋亡信号。
