Death Associated Protein 1: a new ER stress regulator protein

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" Death Associated Protein 1: a new ER stress regulator protein "
Eran Reem A. Kimchi

Document Type	:	Latin Dissertation
Language of Document	:	English
Record Number	:	54060
Doc. No	:	TL24014
Call number	:	‭3510118‬
Main Entry	:	Eran Reem
Title & Author	:	Death Associated Protein 1: a new ER stress regulator protein\ Eran Reem
College	:	The Weizmann Institute of Science (Israel)
Date	:	2009
Degree	:	Ph.D.
student score	:	2009
Page No	:	60
Abstract	:	Accumulation of unfolded proteins induces endoplasmic reticulum (ER) stress. Excessive and prolonged periods of ER stress leads to apoptosis. In this work we investigated the involvement of Death Associated Protein 1 (DAP1) in ER stress cellular responses and the associated cell death pathways. DAP1 is a small, ubiquitously expressed proline rich protein, highly conserved in evolution. It was isolated by an antisense-based genetic screen aimed at identifying positive mediators of IFN-γ-induced cell death in a mammalian system. In our work we found that DAP1 protein levels and phosphorylation state are regulated in response to a verity of stress. Here we determined the intracellular localization of DAP1 as well as its regulation and function in the ER cellular stress response. Using biochemical fractionations and immunofluorescent staining, we found that DAP1 is localized to the cytosolic side of the ER. It is a phospho protein, which in response to ER stress undergoes rapid de-phosphorylation, followed by an up regulation of the protein steady sate levels. In parallel we determined that DAP1 is also subjected to miRNA repression. The knock down of DAP1 by transfection with shRNA enhances the caspase-mediated apoptotic cell death caused by ER stress. The accelerated death is preceded by a faster and stronger activation of the unfolded Protein Response (UPR). As a result of this study, we propose that DAP1 is a novel regulator of the ER stress response.
Subject	:	Biological sciences; Cell death; Death associated protein 1; ER stress regulator protein; Endoplasmic reticulum stress; Genetics; Cellular biology; 0369:Genetics; 0379:Cellular biology
Added Entry	:	A. Kimchi
Added Entry	:	The Weizmann Institute of Science (Israel)