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: In addition to detectable expression of MOAP-1 in NHBE, hTERT (immortalized with human telomerase), and MCF-10A, we can also detect MOAP-1 in other nontransformed cell lines such as HEMA-LP and PNT1A (Fig. 3, A–C). MOAP-1 protein was reduced or absent in many cancer cells as shown in Figs. 2D and 3. Noticeably, MOAP-1 expression was detected in the p53-positive cell lines (U2OS, HCT116, ZR-75, IMR-32, and PANC1) but was reduced/absent in p53- cells (SAOS-2 and SKOV3), p53 frameshift mutation or rearrangement cell lines (Caco-2 and CAPAN-2), and p53-mutant cell lines (SKBR3, MDA-MB-468, MDA MB-231,BT-549, and BT-20 (breast cancer cells) (Fig. 2D), and OVCAR-3 (ovarian cancer). However, the expression of MOAP-1 did not always correlate with the status of p53 as SW480 (p53-) has detectable MOAP-1, whereas the p53 wild type cell lines, A549, and the majority of the neuroblastoma cell lines do not have robust detection of MOAP-1. Among the cell lines that are p53+/+MOAP-1−/−, all have epigenetic silencing of RASSF1A (12). Therefore, we suspect that RASSF1A may influence the expression of MOAP-1, and we are currently exploring this unexpected observation. The dual loss of MOAP-1 and RASSF1A expression may contribute to malignant cell growth in the solid cancers.