Identification of proteomic changes induced in anaplastic lymphoma kinase-positive anaplastic large cell lymphoma in response to the heat shock protein 90 inhibitor geldanamycin

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Title Identification of proteomic changes induced in anaplastic lymphoma kinase-positive anaplastic large cell lymphoma in response to the heat shock protein 90 inhibitor geldanamycin
Publication Type thesis
School or College School of Medicine
Department Pathology
Author Schumacher, Jonathan A.
Date 2005-12
Description Anaplastic large cell lymphoma (ALCL) is a subset of non-Hodgkin lymphoma that commonly express the t(2;5)(p23;q35) chromosomal translocation, resulting in overexpression of the nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) oncoprotein. ALK harbors a cytoplasmic tyrosine kinase domain that has been shown to associate with and phosphorylate a number of adaptor proteins that initiate transcription signaling and inhibit apoptosis. Heat shock protein 90 (Hsp90) is a molecular chaperone involved in folding of a variety of substrate proteins including p53, Akt/PKB, and NPM-ALK. Geldanamycin (GA) is a benzoquinone ansamycin that binds to and inhibits heat shock protein 90 (Hsp90) from performing its chaperone duties, resulting in ubiquitin-mediated proteasomal degradation of unfolded client proteins. Here we describe a study directed at identifying the molecular mechanisms and establishing some of the proteomic changes induced in NPM-ALK-overexpressing cells due to GA inhibition of Hsp90 function. Our results demonstrate that GA induces G2/M cell cycle arrest and caspase-3 mediated apoptosis. Furthermore, proteomic analysis identified a total of 176 differentially expressed proteins including novel proteins previously unassociated with NPM-ALK survival. Our studies demonstrate some of the molecular mechanisms and novel proteomic changes in NPM-ALK-overexpressing cells induced by GA inhibition of Hsp90.
Type Text
Publisher University of Utah
Subject Physiology
Subject MESH Lymphoma; Heat-Shock Proteins
Dissertation Institution University of Utah
Dissertation Name MS
Language eng
Relation is Version of Digital reproduction of "Identification of proteomic changes induced in anaplastic lymphoma kinase-positive anaplastic large cell lymphoma in response to the heat shock protein 90 inhibitor geldanamycin." Spencer S. Eccles Health Sciences Library.
Rights Management © Jonathan A. Schumacher.
Format application/pdf
Format Medium application/pdf
Format Extent 1,645,813 bytes
Identifier undthes,3974
Source Original University of Utah Spencer S. Eccles Health Sciences Library (no longer available)
Funding/Fellowship ARUP Institute for Clinical and Experimental Pathology
Master File Extent 1,645,843 bytes
ARK ark:/87278/s65t3n8x
Setname ir_etd
ID 190620
Reference URL https://collections.lib.utah.edu/ark:/87278/s65t3n8x
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