Modulator of apoptosis 1 (MOAP-1) is a tumor suppressor protein linked to the RASSF1A protein.

Abstract

Modulator of apoptosis 1 (MOAP-1) is a BH3-like protein that plays key roles in cell death or apoptosis. 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. In this study, we present several lines of evidence from cancer databases, immunoblotting of cancer cells, proliferation, and xenograft assays as well as DNA microarray analysis to demonstrate the role of MOAP-1 as a tumor suppressor protein. Frequent loss of MOAP-1 expression, in at least some cancers, appears to be attributed to mRNA down-regulation and the rapid proteasomal degradation of MOAP-1 that could be reversed utilizing the proteasome inhibitor MG132. 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. The loss of RASSF1A (an upstream regulator of MOAP-1) is one of the earliest detectable epigenetically silenced tumor suppressor proteins in cancer, 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 tumorigenesis.

• Authors: Jennifer Law, Mohamed Salla, Alaa Zare, Yoke Wong, Le Luong, Natalia Volodko, Orysya Svystun, Kayla Flood, Jonathan Lim, Miranda Sung, Jason R B Dyck, Chong Teik Tan, Yu-Chin Su, Victor C Yu, John Mackey, Shairaz Baksh
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 290 Issue 40 Pg. 24100-18 (Oct 02 2015) ISSN: 1083-351X [Electronic] United States
• PMID: 26269600 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• Adaptor Proteins, Signal Transducing
• Apoptosis Regulatory Proteins
• BAX protein, human
• MOAP1 protein, human
• RASSF1 protein, human
• Tumor Suppressor Proteins
• Ubiquitin
• bcl-2-Associated X Protein

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Animals
• Apoptosis
• Apoptosis Regulatory Proteins (metabolism)
• Breast Neoplasms (metabolism)
• Carcinogenesis
• Cell Line, Tumor
• Cell Proliferation
• DNA Damage
• Epigenesis, Genetic
• Female
• Gene Expression Regulation
• Genes, Tumor Suppressor
• Genome-Wide Association Study
• Humans
• Kaplan-Meier Estimate
• Male
• Mice
• Mice, Nude
• Neoplasm Transplantation
• Neoplasms (metabolism)
• Oligonucleotide Array Sequence Analysis
• Protein Binding
• Protein Structure, Tertiary
• Tumor Suppressor Proteins (metabolism)
• Ubiquitin (chemistry)
• bcl-2-Associated X Protein (metabolism)