Modulator of Apoptosis 1 (MOAP-1) is a highly regulated tumor suppressor protein

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. It is an integral partner to the tumor suppressor 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 is yet to be determined. In this study, we present several lines of evidence from cancer databases, immnoblotting of cancer cells, proliferation and xenograft assays to demonstrate the role of MOAP-1 as a tumor suppressor. MOAP-1 overexpressed tumors display upregulation of multiple genes including several pro-apoptotic members that may influence the role of MOAP-1 in cell death. Frequent loss of MOAP-1 expression, in at least some cancers, appears to be attributed to enhanced proteasomal degradation. The loss of RASSF1A is an early marker of tumorigenesis and we speculate that the additional loss of function of MOAP-1 may be a second “hit” to functionally compromise the RASSF1A/MOAP-1 death receptor dependent pathway and drive tumorigensis. RNA was isolated mouse xenographs generated with the HCT116 cell line transfected with wild type Myc-tagged MOAP-1, empty Vector or the Myc-tagged MOAP-1 mutants K278R or K264R in triplicate. Pairwise gene expression differences were compared the two samples. Features selected had more than 1.5-fold up-or down-regulated (P values of >05, unpaired Student’s t-test).