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: Finally, modulators of gene expression were also differentially regulated in the presence of overexpressed MOAP-1. These include serum-response factor, E-26-like protein 1 (ELK1) transcription factor, and signal transducer and activator of transcription 3 (STAT3, validated in Fig. 10C). We were also able to validate the increase in both STAT3 and STAT5a, GNB2L1/RACK1, PTEN, and PARP (all validated in Fig. 10C) in xenograft-derived tumor lysates overexpressing MOAP-1, although the receptor for the STATs, Janus kinase 1 (JAK1), did not appear to be up-regulated (confirmed in Fig. 10C). Interestingly, the overexpression of MOAP-1 also resulted in modulation of key elements linked to metabolism and the Warburg effect (40–42). These include insulin receptor β, AMPK, and pyruvate kinase M2 (PKM2) (validated in Fig. 10C). MOAP-1 may thus have a role in modulating the appearance of biomarkers of the Warburg effect and in modulating metabolic pathways. Overall, our GWAS results suggest that MOAP-1 functions as more than just a pro-apoptotic protein and may be involved in numerous other aspects of homeostatic regulation in colon epithelial cells (Fig. 11).