Grb2 Is Regulated by Foxd3 and Has Roles in Preventing Accumulation and Aggregation of Mutant HuntingtinReportar como inadecuado




Grb2 Is Regulated by Foxd3 and Has Roles in Preventing Accumulation and Aggregation of Mutant Huntingtin - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

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.



Autor: Shounak Baksi, Nihar R. Jana, Nitai Pada Bhattacharyya, Debashis Mukhopadhyay

Fuente: http://plos.srce.hr/



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