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

Law J, Salla M, Zare A, Wong Y, Luong L, Volodko N, Svystun O, Flood K, Lim J, Sung M, Dyck JR, Tan CT, Su YC, Yu VC, Mackey J, Baksh S - J. Biol. Chem. (2015)

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.

View Article: PubMed Central - PubMed

Affiliation: From the Departments of Biochemistry and.

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MOAP-1 is rapidly turned over in several human cancer cell lines. Immunoblotting (IB) for MOAP-1 was performed in selected cell lines by the addition of the proteosome inhibitor, MG132, at a concentration of 10 μm for the indicated times.
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Figure 4: MOAP-1 is rapidly turned over in several human cancer cell lines. Immunoblotting (IB) for MOAP-1 was performed in selected cell lines by the addition of the proteosome inhibitor, MG132, at a concentration of 10 μm for the indicated times.

Mentions: Exon sequencing revealed no mutations in MOAP-1 in several cancer lines investigated, including HCT116 colon cancer cells, H1299 small cell lung cancer, and MDA-MB-231 breast cancer cells. Quantitative PCR revealed decreased mRNA production for MOAP-1 in several cancer cells and patient tumor tissues (Figs. 1D and 2C). It is known that MOAP-1 appears to be highly turned over every 25 min via the ubiquitin-mediated proteasomal degradation (5) and thus may explain lack of detection. If MOAP-1 is regulated by ubiquitin-directed degradation, then the proteasome inhibitor, MG-132, should inhibit the degradation of MOAP-1 and stabilize its expression. Indeed, we can observe this with MG-132 treatment of several cell lines that initially did not reveal detectable MOAP-1 expression, including MDA-MB-468, MDA-MB-231, MCF-7, A549, and A2058 (Fig. 4). For the most part, MOAP-1 ubiquitination can be detected in most of the cell lines in Fig. 4 (data not shown) and are in line with the observations of Lee et al. (5). This would suggest that ubiquitin-directed modulation of MOAP-1 expression can occur in several cancers. Curiously, under MG-132 treatment, MOAP-1 expression in SKOV3 cells is barely detectable for unknown reasons. These experiments reveal the complexity of MOAP-1 regulation. We are currently investigating the importance of ubiquitination for MOAP-1 biology, the mechanism by which this occurs, and characterizing the importance of two identified E3 ligase interacting proteins with MOAP-1 and how they may control the biology of MOAP-1.


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

Law J, Salla M, Zare A, Wong Y, Luong L, Volodko N, Svystun O, Flood K, Lim J, Sung M, Dyck JR, Tan CT, Su YC, Yu VC, Mackey J, Baksh S - J. Biol. Chem. (2015)

MOAP-1 is rapidly turned over in several human cancer cell lines. Immunoblotting (IB) for MOAP-1 was performed in selected cell lines by the addition of the proteosome inhibitor, MG132, at a concentration of 10 μm for the indicated times.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4591801&req=5

Figure 4: MOAP-1 is rapidly turned over in several human cancer cell lines. Immunoblotting (IB) for MOAP-1 was performed in selected cell lines by the addition of the proteosome inhibitor, MG132, at a concentration of 10 μm for the indicated times.
Mentions: Exon sequencing revealed no mutations in MOAP-1 in several cancer lines investigated, including HCT116 colon cancer cells, H1299 small cell lung cancer, and MDA-MB-231 breast cancer cells. Quantitative PCR revealed decreased mRNA production for MOAP-1 in several cancer cells and patient tumor tissues (Figs. 1D and 2C). It is known that MOAP-1 appears to be highly turned over every 25 min via the ubiquitin-mediated proteasomal degradation (5) and thus may explain lack of detection. If MOAP-1 is regulated by ubiquitin-directed degradation, then the proteasome inhibitor, MG-132, should inhibit the degradation of MOAP-1 and stabilize its expression. Indeed, we can observe this with MG-132 treatment of several cell lines that initially did not reveal detectable MOAP-1 expression, including MDA-MB-468, MDA-MB-231, MCF-7, A549, and A2058 (Fig. 4). For the most part, MOAP-1 ubiquitination can be detected in most of the cell lines in Fig. 4 (data not shown) and are in line with the observations of Lee et al. (5). This would suggest that ubiquitin-directed modulation of MOAP-1 expression can occur in several cancers. Curiously, under MG-132 treatment, MOAP-1 expression in SKOV3 cells is barely detectable for unknown reasons. These experiments reveal the complexity of MOAP-1 regulation. We are currently investigating the importance of ubiquitination for MOAP-1 biology, the mechanism by which this occurs, and characterizing the importance of two identified E3 ligase interacting proteins with MOAP-1 and how they may control the biology of MOAP-1.

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.

View Article: PubMed Central - PubMed

Affiliation: From the Departments of Biochemistry and.

Show MeSH
Related in: MedlinePlus