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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todo:paper_19326203_v12_n5_p_Laiseca2023-10-03T16:34:49Z Functional interaction between co-expressed MAGE-A proteins Laiseca, J.E. Ladelfa, M.F. Cotignola, J. Peche, L.Y. Pascucci, F.A. Castaño, B.A. Galigniana, M.D. Schneider, C. Monte, M. 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar 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 |
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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 Laiseca, J.E. Ladelfa, M.F. Cotignola, J. Peche, L.Y. Pascucci, F.A. Castaño, B.A. Galigniana, M.D. Schneider, C. Monte, M. 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. |
format |
JOUR |
author |
Laiseca, J.E. Ladelfa, M.F. Cotignola, J. Peche, L.Y. Pascucci, F.A. Castaño, B.A. Galigniana, M.D. Schneider, C. Monte, M. |
author_facet |
Laiseca, J.E. Ladelfa, M.F. Cotignola, J. Peche, L.Y. Pascucci, F.A. Castaño, B.A. Galigniana, M.D. Schneider, C. Monte, M. |
author_sort |
Laiseca, J.E. |
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 |
url |
http://hdl.handle.net/20.500.12110/paper_19326203_v12_n5_p_Laiseca |
work_keys_str_mv |
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_version_ |
1782025990109659136 |