Functions of the pointed domain within the ETS gene family

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Publication Type dissertation
School or College School of Medicine
Department Oncological Sciences
Author Seidel, Jeffrey John
Title Functions of the pointed domain within the ETS gene family
Date 2001-12
Description All members of the ets family of transcription factors conserve the DNA binding ETS domain that recognizes the core sequence 5'-GGA(A/T)-3'. Despite conserving this domain, individual ets proteins can perform specific functions. Many unique features exist among ets proteins that establish this diversity. One feature, the Pointed (PNT) domain, is a region of 80 amino acids conserved among only a subset of ets proteins. The function of the PNT domain is not clear, but it is proposed to mediate hemotypic and heterotypic protein-protein interactions. This thesis investigates the function of the PNT domain of four ets proteins. Surprisingly, this domain was found to serve different functions within the family. First, PNT domains can have different oligomeriazation states. The Fts-1 PNT domain, composed of five alph helices that assume a globular fold, is monomeric in solution. In contrast, the PNT domain of the ets family member TEL formed multimers under a variety of in vitro conditions. Second, PNT domains have different protein partners. In an affinity chromatography experiment, a fragments of Ets-1 spanning the PNT domain an MAPK site bound the mitogen-activated protein kinases (MAPKs) ERK1 and/or ERK2. These kinases phosphorylate Ets-1 and Ets-2 at a MAPK site N-terminal to the PNT domain. Kinase assays identified docking site on the surface of the PNT domain of Ets-1 important for interacting with ERK2 and Ras/MAPK signaling. The docking site is conserved in sequence and in function in the PNT domain of Ets-2 but not in the PNT domain of the ets family member GABPalph. The docking site sequence is also not well-conserved in other PNT domains. These results highlight the PNT domain as a conserved structureal element whose distinct surface features generate specificity of function among ets proteins.
Type Text
Publisher University of Utah
Subject Transcription Factors
Subject MESH Plasmids; Gene Expression; Gene Expression Regulation; Proteins
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "Functions of the pointed domain within the ETS gene family." Spencer S. Eccles Health Sciences Library. Print version of "Functions of the pointed domain within the ETS gene family." available at J. Willard Marriott Library Special Collection. QP6.5 2001 .S44.
Rights Management © Jeffrey John Seidel
Format Medium application/pdf
Format Extent 3,133,895 bytes
Identifier undthes,4716
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
Funding/Fellowship Predoctoral fellowship from the Cancer Training Grant and National Institutes of Health
Master File Extent 3,133,959 bytes
ARK ark:/87278/s6x3507z
Setname ir_etd
Date Created 2012-04-24
Date Modified 2012-04-24
ID 190653
Reference URL https://collections.lib.utah.edu/ark:/87278/s6x3507z