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Emerging Roles of MTG16 in Cell-Fate Control of Hematopoietic Stem Cells and Cancer

MTG16 (myeloid translocation gene on chromosome 16) and its related proteins, MTG8 and MTGR1, define a small family of transcriptional corepressors. These corepressors share highly conserved domain structures yet have distinct biological functions and tissue specificity. In vivo studies have shown t...

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Detalles Bibliográficos
Autores principales: Steinauer, Nickolas, Guo, Chun, Zhang, Jinsong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735743/
https://www.ncbi.nlm.nih.gov/pubmed/29358956
http://dx.doi.org/10.1155/2017/6301385
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author Steinauer, Nickolas
Guo, Chun
Zhang, Jinsong
author_facet Steinauer, Nickolas
Guo, Chun
Zhang, Jinsong
author_sort Steinauer, Nickolas
collection PubMed
description MTG16 (myeloid translocation gene on chromosome 16) and its related proteins, MTG8 and MTGR1, define a small family of transcriptional corepressors. These corepressors share highly conserved domain structures yet have distinct biological functions and tissue specificity. In vivo studies have shown that, of the three MTG corepressors, MTG16 is uniquely important for the regulation of hematopoietic stem/progenitor cell (HSPC) proliferation and differentiation. Apart from this physiological function, MTG16 is also involved in carcinomas and leukemias, acting as the genetic target of loss of heterozygosity (LOH) aberrations in breast cancer and recurrent translocations in leukemia. The frequent involvement of MTG16 in these disease etiologies implies an important developmental role for this transcriptional corepressor. Furthermore, mounting evidence suggests that MTG16 indirectly alters the disease course of several leukemias via its regulatory interactions with a variety of pathologic fusion proteins. For example, a recent study has shown that MTG16 can repress not only wild-type E2A-mediated transcription, but also leukemia fusion protein E2A-Pbx1-mediated transcription, suggesting that MTG16 may serve as a potential therapeutic target in acute lymphoblastic leukemia expressing the E2A-Pbx1 fusion protein. Given that leukemia stem cells share similar regulatory pathways with normal HSPCs, studies to further understand how MTG16 regulates cell proliferation and differentiation could lead to novel therapeutic approaches for leukemia treatment.
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spelling pubmed-57357432018-01-22 Emerging Roles of MTG16 in Cell-Fate Control of Hematopoietic Stem Cells and Cancer Steinauer, Nickolas Guo, Chun Zhang, Jinsong Stem Cells Int Review Article MTG16 (myeloid translocation gene on chromosome 16) and its related proteins, MTG8 and MTGR1, define a small family of transcriptional corepressors. These corepressors share highly conserved domain structures yet have distinct biological functions and tissue specificity. In vivo studies have shown that, of the three MTG corepressors, MTG16 is uniquely important for the regulation of hematopoietic stem/progenitor cell (HSPC) proliferation and differentiation. Apart from this physiological function, MTG16 is also involved in carcinomas and leukemias, acting as the genetic target of loss of heterozygosity (LOH) aberrations in breast cancer and recurrent translocations in leukemia. The frequent involvement of MTG16 in these disease etiologies implies an important developmental role for this transcriptional corepressor. Furthermore, mounting evidence suggests that MTG16 indirectly alters the disease course of several leukemias via its regulatory interactions with a variety of pathologic fusion proteins. For example, a recent study has shown that MTG16 can repress not only wild-type E2A-mediated transcription, but also leukemia fusion protein E2A-Pbx1-mediated transcription, suggesting that MTG16 may serve as a potential therapeutic target in acute lymphoblastic leukemia expressing the E2A-Pbx1 fusion protein. Given that leukemia stem cells share similar regulatory pathways with normal HSPCs, studies to further understand how MTG16 regulates cell proliferation and differentiation could lead to novel therapeutic approaches for leukemia treatment. Hindawi 2017 2017-11-22 /pmc/articles/PMC5735743/ /pubmed/29358956 http://dx.doi.org/10.1155/2017/6301385 Text en Copyright © 2017 Nickolas Steinauer et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Steinauer, Nickolas
Guo, Chun
Zhang, Jinsong
Emerging Roles of MTG16 in Cell-Fate Control of Hematopoietic Stem Cells and Cancer
title Emerging Roles of MTG16 in Cell-Fate Control of Hematopoietic Stem Cells and Cancer
title_full Emerging Roles of MTG16 in Cell-Fate Control of Hematopoietic Stem Cells and Cancer
title_fullStr Emerging Roles of MTG16 in Cell-Fate Control of Hematopoietic Stem Cells and Cancer
title_full_unstemmed Emerging Roles of MTG16 in Cell-Fate Control of Hematopoietic Stem Cells and Cancer
title_short Emerging Roles of MTG16 in Cell-Fate Control of Hematopoietic Stem Cells and Cancer
title_sort emerging roles of mtg16 in cell-fate control of hematopoietic stem cells and cancer
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5735743/
https://www.ncbi.nlm.nih.gov/pubmed/29358956
http://dx.doi.org/10.1155/2017/6301385
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