%0 Journal Article
%T Modulator of Apoptosis 1: A Highly Regulated RASSF1A-Interacting BH3-Like Protein
%A Jennifer Law
%A Victor C. Yu
%A Shairaz Baksh
%J Molecular Biology International
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/536802
%X Modulator of apoptosis 1 (MOAP-1) is a BH3-like protein that plays key roles in both the intrinsic and extrinsic modes of cell death or apoptosis. MOAP-1 is part of the Ras association domain family 1A (RASSF1A)/MOAP-1 pro-apoptotic extrinsic signaling pathway that regulates apoptosis by utilizing death receptors such as tumor necrosis factor ¦Á (TNF¦Á) or TNF-related apoptosis-inducing ligand (TRAIL) to inhibit abnormal growth. RASSF1A is a bona fide tumor suppressor gene that is epigenetically silenced by promoter-specific methylation in numerous human cancers. MOAP-1 is a downstream effector of RASSF1A that promotes Bax activation and cell death and is highly regulated during apoptosis. We speculate that MOAP-1 and RASSF1A are important elements of an ¡°apoptotic checkpoint¡± that directly influences the outcome of cell death. The failure to regulate this pro-apoptotic pathway may result in the appearance of cancer and possibly other disorders. Although loss of RASSF1A expression is frequently observed in human cancers, it is currently unknown if MOAP-1 expression may also be affected during carcinogenesis to result in uncontrolled malignant growth. In this article, we will summarize what is known about the biological role(s) of MOAP-1 and how it functions as a downstream effector to RASSF1A. 1. Introduction Cancer is a disease of uncontrolled cell proliferation and is the third leading causing of death worldwide following cardiovascular and infectious diseases [2]. The abnormal proliferation of cells during cancer development results from a multistep process involving the deregulation of genes that promote cell growth (oncogenes) and those that normally function to restrain growth (tumor suppressors). Interestingly, approximately 90% of the genes that are associated with cancer development have now been identified as being tumor suppressors [3]. Moreover, many of these growth inhibitory genes encode proteins that are involved in cell death. RASSF1A has multiple biological functions including the regulation of Bax-mediated cell death [4¨C6]. MOAP-1, a highly regulated pro-apoptotic protein, serves a critical role during mitochondrial-dependent apoptosis by influencing and sustaining Bax activation [7, 8]. In this review, we will discuss how MOAP-1 is regulated and how it serves as a pivotal RASSF1A effector protein to regulate cell death. 2. Apoptosis: A Regulated Biological Process to Modulate Growth A well-known mechanism of tumor suppression is the elimination of unwanted cells through a sequence of events known as apoptosis [9]. The significance of
%U http://www.hindawi.com/journals/mbi/2012/536802/