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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Autor principal:	Ladelfa, María Fátima
Publicado:	2017
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:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v12_n5_p_Laiseca 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

id	paper:paper_19326203_v12_n5_p_Laiseca
record_format	dspace
spelling	paper:paper_19326203_v12_n5_p_Laiseca2023-06-08T16:30:40Z Functional interaction between co-expressed MAGE-A proteins Ladelfa, María Fátima 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 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. Fil:Ladelfa, M.F. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2017 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v12_n5_p_Laiseca http://hdl.handle.net/20.500.12110/paper_19326203_v12_n5_p_Laiseca
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	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
spellingShingle	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 Ladelfa, María Fátima Functional interaction between co-expressed MAGE-A proteins
topic_facet	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
description	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.
author	Ladelfa, María Fátima
author_facet	Ladelfa, María Fátima
author_sort	Ladelfa, María Fátima
title	Functional interaction between co-expressed MAGE-A proteins
title_short	Functional interaction between co-expressed MAGE-A proteins
title_full	Functional interaction between co-expressed MAGE-A proteins
title_fullStr	Functional interaction between co-expressed MAGE-A proteins
title_full_unstemmed	Functional interaction between co-expressed MAGE-A proteins
title_sort	functional interaction between co-expressed mage-a proteins
publishDate	2017
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v12_n5_p_Laiseca http://hdl.handle.net/20.500.12110/paper_19326203_v12_n5_p_Laiseca
work_keys_str_mv	AT ladelfamariafatima functionalinteractionbetweencoexpressedmageaproteins
_version_	1768542523790196736

Functional interaction between co-expressed MAGE-A proteins

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