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
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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