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Adenomatous polyposis coli protein contains two nuclear export signals and shuttles between the nucleus and cytoplasm.

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Adenomatous polyposis coli protein contains two nuclear export signals and shuttles between the nucleus and cytoplasm.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Neufeld, K. L. Bogerd, H. Kang, Y. Beckerle, M. C. Cullen, B. R. Nix, D. A. White, R. L.
Description	Author Affiliation: Neufeld KL ( Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112, USA. kristi.neufeld@hci.utah.edu);
Abstract	Mutational inactivation of the adenomatous polyposis coli (APC) tumor suppressor initiates most hereditary and sporadic colon carcinomas. Although APC protein is located in both the cytoplasm and the nucleus, the protein domains required to maintain a predominantly cytoplasmic localization are unknown. Here, we demonstrate that nuclear export of APC is mediated by two intrinsic, leucine-rich, nuclear export signals (NESs) located near the amino terminus. Each NES was able to induce the nuclear export of a fused carrier protein. Both APC NESs were independently able to interact with the Crm1 nuclear export factor and substitute for the HIV-1 Rev NES to mediate nuclear mRNA export. Both APC NESs functioned within the context of APC sequence: an amino-terminal APC peptide containing both NESs interacted with Crm1 and showed nuclear export in a heterokaryon nucleocytoplasmic shuttling assay. Also, mutation of both APC NESs resulted in the nuclear accumulation of the full-length, approximately 320-kDa APC protein, further establishing that the two intrinsic APC NESs are necessary for APC protein nuclear export. Moreover, endogenous APC accumulated in the nucleus of cells treated with the Crm1-specific nuclear export inhibitor leptomycin B. Together, these data indicate that APC is a nucleocytoplasmic shuttle protein whose predominantly cytoplasmic localization requires NES function and suggests that APC may be important for signaling between the nuclear and cytoplasmic compartments of epithelial cells.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	22
Volume Number	97
Language	English
Publisher	National Academy of Sciences
Publisher Date	2000-11-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cell Nucleus Metabolism Cytoplasm Cytoskeletal Proteins Genetics Protein Sorting Signals Adenomatous Polyposis Coli Protein Amino Acid Sequence Animals Cell Line Chemistry Molecular Sequence Data Sequence Homology, Amino Acid Signal Transduction Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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