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BAG1: The Guardian of Anti-Apoptotic Proteins in Acute Myeloid Leukemia

BCL2 associated Athano-Gene 1 (BAG1) is a multifunctional protein that has been described to be involved in different cell processes linked to cell survival. It has been reported as deregulated in diverse cancer types. Here, BAG1 protein was found highly expressed in children with acute myeloid leuk...

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Autores principales: Aveic, Sanja, Pigazzi, Martina, Basso, Giuseppe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189928/
https://www.ncbi.nlm.nih.gov/pubmed/22016818
http://dx.doi.org/10.1371/journal.pone.0026097
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author Aveic, Sanja
Pigazzi, Martina
Basso, Giuseppe
author_facet Aveic, Sanja
Pigazzi, Martina
Basso, Giuseppe
author_sort Aveic, Sanja
collection PubMed
description BCL2 associated Athano-Gene 1 (BAG1) is a multifunctional protein that has been described to be involved in different cell processes linked to cell survival. It has been reported as deregulated in diverse cancer types. Here, BAG1 protein was found highly expressed in children with acute myeloid leukemia at diagnosis, and in a cohort of leukemic cell lines. A silencing approach was used for determining BAG1's role in AML, finding that its down-regulation decreased expression of BCL2, BCL-XL, MCL1, and phospho-ERK1/2, all proteins able to sustain leukemia, without affecting the pro-apoptotic protein BAX. BAG1 down-regulation was also found to increase expression of BAG3, whose similar activity was able to compensate the loss of function of BAG1. BAG1/BAG3 co-silencing caused an enhanced cell predisposition to death in cell lines and also in primary AML cultures, affecting the same proteins. Cell death was CASPASE-3 dependent, was accompanied by PARP cleavage and documented by an increased release of pro-apoptotic molecules Smac/DIABLO and Cytochrome c. BAG1 was found to directly maintain BCL2 and to protect MCL1 from proteasomal degradation by controlling USP9X expression, which appeared to be its novel target. Finally, BAG1 was found able to affect leukemia cell fate by influencing the expression of anti-apoptotic proteins crucial for AML maintenance.
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spelling pubmed-31899282011-10-20 BAG1: The Guardian of Anti-Apoptotic Proteins in Acute Myeloid Leukemia Aveic, Sanja Pigazzi, Martina Basso, Giuseppe PLoS One Research Article BCL2 associated Athano-Gene 1 (BAG1) is a multifunctional protein that has been described to be involved in different cell processes linked to cell survival. It has been reported as deregulated in diverse cancer types. Here, BAG1 protein was found highly expressed in children with acute myeloid leukemia at diagnosis, and in a cohort of leukemic cell lines. A silencing approach was used for determining BAG1's role in AML, finding that its down-regulation decreased expression of BCL2, BCL-XL, MCL1, and phospho-ERK1/2, all proteins able to sustain leukemia, without affecting the pro-apoptotic protein BAX. BAG1 down-regulation was also found to increase expression of BAG3, whose similar activity was able to compensate the loss of function of BAG1. BAG1/BAG3 co-silencing caused an enhanced cell predisposition to death in cell lines and also in primary AML cultures, affecting the same proteins. Cell death was CASPASE-3 dependent, was accompanied by PARP cleavage and documented by an increased release of pro-apoptotic molecules Smac/DIABLO and Cytochrome c. BAG1 was found to directly maintain BCL2 and to protect MCL1 from proteasomal degradation by controlling USP9X expression, which appeared to be its novel target. Finally, BAG1 was found able to affect leukemia cell fate by influencing the expression of anti-apoptotic proteins crucial for AML maintenance. Public Library of Science 2011-10-10 /pmc/articles/PMC3189928/ /pubmed/22016818 http://dx.doi.org/10.1371/journal.pone.0026097 Text en Aveic et al. http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Aveic, Sanja
Pigazzi, Martina
Basso, Giuseppe
BAG1: The Guardian of Anti-Apoptotic Proteins in Acute Myeloid Leukemia
title BAG1: The Guardian of Anti-Apoptotic Proteins in Acute Myeloid Leukemia
title_full BAG1: The Guardian of Anti-Apoptotic Proteins in Acute Myeloid Leukemia
title_fullStr BAG1: The Guardian of Anti-Apoptotic Proteins in Acute Myeloid Leukemia
title_full_unstemmed BAG1: The Guardian of Anti-Apoptotic Proteins in Acute Myeloid Leukemia
title_short BAG1: The Guardian of Anti-Apoptotic Proteins in Acute Myeloid Leukemia
title_sort bag1: the guardian of anti-apoptotic proteins in acute myeloid leukemia
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189928/
https://www.ncbi.nlm.nih.gov/pubmed/22016818
http://dx.doi.org/10.1371/journal.pone.0026097
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