Modulator of apoptosis 1 (MOAP-1) is a tumor suppressor protein linked to the RASSF1A protein
Autor: | Mohamed Salla, N. V. Volodko, Victor C. Yu, Shairaz Baksh, John R. Mackey, Jennifer Law, Yoke Wong, Le Luong, Chong Teik Tan, Orysya Svystun, Alaa Zare, Jonathan Lim, Kayla Flood, Yu-Chin Su, Jason R.B. Dyck, Miranda Sung |
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Rok vydání: | 2015 |
Předmět: |
Male
Carcinogenesis Apoptosis Kaplan-Meier Estimate medicine.disease_cause Biochemistry Epigenesis Genetic Mice Neoplasms E2F1 GWAS SOCS6 Genes Tumor Suppressor ubiquitylation (ubiquitination) tumor suppressor gene Oligonucleotide Array Sequence Analysis bcl-2-Associated X Protein Rassf1a moap-1 Cell biology GPS2 Female Protein Binding Signal Transduction Tumor suppressor gene Mice Nude Breast Neoplasms Biology Retinoblastoma-like protein 1 Bcl-2-associated X protein Cell Line Tumor medicine Animals Humans cancer Molecular Biology Adaptor Proteins Signal Transducing Cell Proliferation Ubiquitin Tumor Suppressor Proteins Cell Biology Protein Structure Tertiary Merlin (protein) Gene Expression Regulation tubulin Bax biology.protein Apoptosis Regulatory Proteins Neoplasm Transplantation DNA Damage Genome-Wide Association Study |
Zdroj: | The Journal of Biological Chemistry |
ISSN: | 1083-351X |
Popis: | Background: MOAP-1 is a pro-apoptotic protein. Results: MOAP-1 expression is reduced in cancers and high expression correlated with increased patient survival. MOAP-1 can associate with tubulin and modulate tubulin stability. Furthermore, loss of the BH3 domain of MOAP-1 resulted in lack of tumor suppressor function. Conclusion: MOAP-1 is a highly regulated tumor suppressor protein. Significance: The loss of MOAP-1 may significantly contribute to tumorigenesis. 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. |
Databáze: | OpenAIRE |
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