Grb2 is regulated by foxd3 and has roles in preventing accumulation and aggregation of mutant huntingtin.

Growth factor receptor protein binding protein 2 (Grb2) is known to be associated with intracellular growth and proliferation related signaling cascades. Huntingtin (Htt), a ubiquitously expressed protein, when mutated, forms toxic intracellular aggregates - the hallmark of Huntington's disease...

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Autores principales:	Shounak Baksi, Nihar R Jana, Nitai Pada Bhattacharyya, Debashis Mukhopadhyay
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1f16f5c752b7432987ec5eed146c7f2c
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spelling	oai:doaj.org-article:1f16f5c752b7432987ec5eed146c7f2c2021-11-18T08:52:02ZGrb2 is regulated by foxd3 and has roles in preventing accumulation and aggregation of mutant huntingtin.1932-620310.1371/journal.pone.0076792https://doaj.org/article/1f16f5c752b7432987ec5eed146c7f2c2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24116161/?tool=EBIhttps://doaj.org/toc/1932-6203Growth factor receptor protein binding protein 2 (Grb2) is known to be associated with intracellular growth and proliferation related signaling cascades. Huntingtin (Htt), a ubiquitously expressed protein, when mutated, forms toxic intracellular aggregates - the hallmark of Huntington's disease (HD). We observed an elevated expression of Grb2 in neuronal cells in animal and cell models of HD. Grb2 overexpression was predominantly regulated by the transcription factor Forkhead Box D3 (Foxd3). Exogenous expression of Grb2 also reduced aggregation of mutant Htt in Neuro2A cells. Grb2 is also known to interact with Htt, depending on epidermal growth factor receptor (EGFR) activation. Grb2- mutant Htt interaction in the contrary, took place in vesicular structures, independent of EGFR activation that eventually merged with autophagosomes and activated the autophagy machinery helping in autophagosome and lysosome fusion. Grb2, with its emerging dual role, holds promise for a survival mechanism for HD.Shounak BaksiNihar R JanaNitai Pada BhattacharyyaDebashis MukhopadhyayPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 10, p e76792 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shounak Baksi Nihar R Jana Nitai Pada Bhattacharyya Debashis Mukhopadhyay Grb2 is regulated by foxd3 and has roles in preventing accumulation and aggregation of mutant huntingtin.
description	Growth factor receptor protein binding protein 2 (Grb2) is known to be associated with intracellular growth and proliferation related signaling cascades. Huntingtin (Htt), a ubiquitously expressed protein, when mutated, forms toxic intracellular aggregates - the hallmark of Huntington's disease (HD). We observed an elevated expression of Grb2 in neuronal cells in animal and cell models of HD. Grb2 overexpression was predominantly regulated by the transcription factor Forkhead Box D3 (Foxd3). Exogenous expression of Grb2 also reduced aggregation of mutant Htt in Neuro2A cells. Grb2 is also known to interact with Htt, depending on epidermal growth factor receptor (EGFR) activation. Grb2- mutant Htt interaction in the contrary, took place in vesicular structures, independent of EGFR activation that eventually merged with autophagosomes and activated the autophagy machinery helping in autophagosome and lysosome fusion. Grb2, with its emerging dual role, holds promise for a survival mechanism for HD.
format	article
author	Shounak Baksi Nihar R Jana Nitai Pada Bhattacharyya Debashis Mukhopadhyay
author_facet	Shounak Baksi Nihar R Jana Nitai Pada Bhattacharyya Debashis Mukhopadhyay
author_sort	Shounak Baksi
title	Grb2 is regulated by foxd3 and has roles in preventing accumulation and aggregation of mutant huntingtin.
title_short	Grb2 is regulated by foxd3 and has roles in preventing accumulation and aggregation of mutant huntingtin.
title_full	Grb2 is regulated by foxd3 and has roles in preventing accumulation and aggregation of mutant huntingtin.
title_fullStr	Grb2 is regulated by foxd3 and has roles in preventing accumulation and aggregation of mutant huntingtin.
title_full_unstemmed	Grb2 is regulated by foxd3 and has roles in preventing accumulation and aggregation of mutant huntingtin.
title_sort	grb2 is regulated by foxd3 and has roles in preventing accumulation and aggregation of mutant huntingtin.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/1f16f5c752b7432987ec5eed146c7f2c
work_keys_str_mv	AT shounakbaksi grb2isregulatedbyfoxd3andhasrolesinpreventingaccumulationandaggregationofmutanthuntingtin AT niharrjana grb2isregulatedbyfoxd3andhasrolesinpreventingaccumulationandaggregationofmutanthuntingtin AT nitaipadabhattacharyya grb2isregulatedbyfoxd3andhasrolesinpreventingaccumulationandaggregationofmutanthuntingtin AT debashismukhopadhyay grb2isregulatedbyfoxd3andhasrolesinpreventingaccumulationandaggregationofmutanthuntingtin
_version_	1718421189015109632

Grb2 is regulated by foxd3 and has roles in preventing accumulation and aggregation of mutant huntingtin.

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