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
Related in: MedlinePlus
Mentions: Further analysis of several MOAP-1-negative and -positive cells verified the important role of MOAP-1 in growth suppression by promoting apoptosis (Fig. 6). Cells having robust expression of MOAP-1 (HCT116 and HT-29 colon cancer cells) had robust cleavage of poly(ADP-ribose) polymerase (PARP) upon TNFα/CHX (extrinsic pathway) stimulation, whereas cells with reduced or absent endogenous MOAP-1 expression (MDA-MB-468, SKOV3 and H1299 cells) displayed very limited PARP cleavage upon TNFα/CHX stimulation (Fig. 6, A and B). Upon stable re-expression of MOAP-1 in H1299 cells, PARP cleavage was significantly enhanced, and the p85-cleaved form of PARP was detected upon TNFα/CHX addition that appeared to be augmented by the presence of stably expressed RASSF1A and MOAP-1 (Fig. 6C). Furthermore, staurosporine (intrinsic apoptotic pathway stimulation) was also more robust in the presence of stably expressed MOAP-1 in H1299 cells (Fig. 6D). Annexin V staining confirmed our PARP results to illustrate that both early (annexin V staining) and late (PARP cleavage) markers of apoptosis were generated in the presence of MOAP-1 (Fig. 6E). Similar results were obtained for A549 lung cancer cells and SKOV3 ovarian cancer cells (data not shown). Together, these results demonstrate tumor suppressor properties of MOAP1 via repressing cell proliferation and promoting cell death in cancer cell lines.