Regulated nuclear import of the adenomatous polyposis coli protein.

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Title Regulated nuclear import of the adenomatous polyposis coli protein.
Publication Type dissertation
School or College School of Medicine
Department Oncological Sciences
Author Zhang, Fang
Date 2001-08
Description Mutation of the Adenomatous Polyposis Coli (APC) gene is an early step in the development of colorectal carcinomas. To provide clues for APC's role in tumor suppression, the subcellular distribution of APC was studied, and APC was found to localize to both the cytoplasm and the nucleus of normal human epithelial cells. The objectives of this study were to characterize the intrinsic signals that mediate APC nuclear import, examine the regulation of APC's nuclear localization and its mechanism, and study the functional importance of this nuclear localization. Two functional nuclear localization signals (NLSs), NLS1[APC] and NLS2[APC], were identified. They were each sufficient to target the cytoplasmic protein beta-galactosidase to the nucleus, and they were both necessary for optimal nuclear import of full-length APC protein. To analyze how cellular context affects APC distribution, several cellular contexts were examined including cell density, cell cycle, cell-cell contact, and extracellular calcium. We determined that cell density, but not cell cycle, influenced APC's subcellular distribution. Further analysis of the two defined NLSs revealed that the adjacent potential CK2 and PKA sites regulated NLS2[APC]-mediated nuclear import. Phosphorylation at the CK2 site increased and phosphorylation at the PKA site decreased NLS2<sub> APC
Type Text
Publisher University of Utah
Subject Genetics; Proteins
Subject MESH Colon; Colonic Neoplasms
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "Regulated nuclear import of the adenomatous polyposis coli protein." Spencer S. Eccles Health Sciences Library. Print version of "Regulated nuclear import of the adenomatous polyposis coli protein." available at J. Willard Marriott Library Special Collection. RC39.5 2001 .Z48.
Rights Management © Fang Zhang.
Format application/pdf
Format Medium application/pdf
Identifier us-etd2,24701
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available).
ARK ark:/87278/s6g73v8b
Setname ir_etd
ID 192831
Reference URL https://collections.lib.utah.edu/ark:/87278/s6g73v8b
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