Modulator of apoptosis 1 (MOAP-1) is a tumor suppressor protein linked to the RASSF1A protein.
Bottom Line: It is an integral partner to the tumor suppressor protein, Ras association domain family 1A (RASSF1A), and functions to activate the Bcl-2 family pro-apoptotic protein Bax.Although RASSF1A is now considered a bona fide tumor suppressor protein, the role of MOAP-1 as a tumor suppressor protein has yet to be determined.Overexpression of MOAP-1 in several cancer cell lines resulted in reduced tumorigenesis and up-regulation of genes involved in cancer regulatory pathways that include apoptosis (p53, Fas, and MST1), DNA damage control (poly(ADP)-ribose polymerase and ataxia telangiectasia mutated), those within the cell metabolism (IR-α, IR-β, and AMP-activated protein kinase), and a stabilizing effect on microtubules.
Affiliation: From the Departments of Biochemistry and.Show MeSH
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Mentions: Exon sequencing revealed no mutations in MOAP-1 in several cancer lines investigated, including HCT116 colon cancer cells, H1299 small cell lung cancer, and MDA-MB-231 breast cancer cells. Quantitative PCR revealed decreased mRNA production for MOAP-1 in several cancer cells and patient tumor tissues (Figs. 1D and 2C). It is known that MOAP-1 appears to be highly turned over every 25 min via the ubiquitin-mediated proteasomal degradation (5) and thus may explain lack of detection. If MOAP-1 is regulated by ubiquitin-directed degradation, then the proteasome inhibitor, MG-132, should inhibit the degradation of MOAP-1 and stabilize its expression. Indeed, we can observe this with MG-132 treatment of several cell lines that initially did not reveal detectable MOAP-1 expression, including MDA-MB-468, MDA-MB-231, MCF-7, A549, and A2058 (Fig. 4). For the most part, MOAP-1 ubiquitination can be detected in most of the cell lines in Fig. 4 (data not shown) and are in line with the observations of Lee et al. (5). This would suggest that ubiquitin-directed modulation of MOAP-1 expression can occur in several cancers. Curiously, under MG-132 treatment, MOAP-1 expression in SKOV3 cells is barely detectable for unknown reasons. These experiments reveal the complexity of MOAP-1 regulation. We are currently investigating the importance of ubiquitination for MOAP-1 biology, the mechanism by which this occurs, and characterizing the importance of two identified E3 ligase interacting proteins with MOAP-1 and how they may control the biology of MOAP-1.