Functional interaction between co-expressed MAGE-A proteins

MAGE-A (Melanoma Antigen Genes-A) are tumor-associated proteins with expression in a broad spectrum of human tumors and normal germ cells. MAGE-A gene expression and function are being increasingly investigated to better understand the mechanisms by which MAGE proteins collaborate in tumorigenesis a...

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Detalles Bibliográficos
Autores principales: Laiseca, J.E., Ladelfa, M.F., Cotignola, J., Peche, L.Y., Pascucci, F.A., Castaño, B.A., Galigniana, M.D., Schneider, C., Monte, M.
Formato: JOUR
Materias:
androgen receptor
lysine
melanoma antigen
melanoma antigen gene A
melanoma antigen gene A11
melanoma antigen gene A6
proteasome
unclassified drug
Article
controlled study
HEK293T cell line
human
human cell
LNCaP cell line
male
protein degradation
protein domain
protein expression
protein function
protein protein interaction
protein stability
ubiquitination
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_19326203_v12_n5_p_Laiseca
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
Descripción
Sumario:MAGE-A (Melanoma Antigen Genes-A) are tumor-associated proteins with expression in a broad spectrum of human tumors and normal germ cells. MAGE-A gene expression and function are being increasingly investigated to better understand the mechanisms by which MAGE proteins collaborate in tumorigenesis and whether their detection could be useful for disease prognosis purposes. Alterations in epigenetic mechanisms involved in MAGE gene silencing cause their frequent co-expression in tumor cells. Here, we have analyzed the effect of MAGE-A gene co-expression and our results suggest that MageA6 can potentiate the androgen receptor (AR) co-activation function of MageA11. Database search confirmed that MageA11 and MageA6 are co-expressed in human prostate cancer samples. We demonstrate that MageA6 and MageA11 form a protein complex resulting in the stabilization of MageA11 and consequently the enhancement of AR activity. The mechanism involves association of the Mage A6-MHD domain to MageA11, prevention of MageA11 ubiquitinylation on lysines 240 and 245 and decreased proteasome-dependent degradation. We experimentally demonstrate here for the first time that two MAGE-A proteins can act together in a non-redundant way to potentiate a specific oncogenic function. Overall, our results highlight the complexity of the MAGE gene networking in regulating cancer cell behavior. © 2017 Laiseca et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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