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Title: Processing of the human protocadherin Fat1 and translocation of its cytoplasmic domain to the nucleus

Abstract

The giant protein hFat1, a member of the cadherin superfamily, has been proposed to play roles in cerebral development, glomerular slit formation, and also to act as a tumor suppressor, but its mechanisms of action have not been elucidated. To examine functions of the transmembrane and cytoplasmic domains, they were expressed in HEK293 and HeLa cells as chimeric proteins in fusion with EGFP and extracellular domains derived from E-cadherin. Proteins comprising the transmembrane domain localized to the membrane fraction. Deletion of this domain resulted in a predominantly nuclear localization of the cytoplasmic segment of hFat1. Nuclear localization was largely reduced by deletion of a presumed juxta-membrane NLS. Fusion proteins located in the plasma membrane underwent proteolytic processing. In a first proteolytic step, only the extracellular domain was cleaved off. In another step, the cleavage product was released to the cytosol and was also found in a low speed pellet fraction, in accordance with the nuclear localization of the cytoplasmic domain of hFat1.

Authors:
 [1];  [1];  [1];  [1];  [1]
  1. University of Konstanz, Department of Biology, Box M648, D-78547 Constance (Germany)
Publication Date:
OSTI Identifier:
20717618
Resource Type:
Journal Article
Journal Name:
Experimental Cell Research
Additional Journal Information:
Journal Volume: 307; Journal Issue: 1; Other Information: DOI: 10.1016/j.yexcr.2005.03.006; PII: S0014-4827(05)00113-8; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0014-4827
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACETATES; CHIMERAS; HELA CELLS; NEOPLASMS; PHOSPHATES; PROTEINS; PROTEOLYSIS; TRANSLOCATION

Citation Formats

Magg, Thomas, Schreiner, Dietmar, Solis, Gonzalo P, Bade, Ernesto G, and Hofer, Hans Werner. Processing of the human protocadherin Fat1 and translocation of its cytoplasmic domain to the nucleus. United States: N. p., 2005. Web. doi:10.1016/j.yexcr.2005.03.006.
Magg, Thomas, Schreiner, Dietmar, Solis, Gonzalo P, Bade, Ernesto G, & Hofer, Hans Werner. Processing of the human protocadherin Fat1 and translocation of its cytoplasmic domain to the nucleus. United States. https://doi.org/10.1016/j.yexcr.2005.03.006
Magg, Thomas, Schreiner, Dietmar, Solis, Gonzalo P, Bade, Ernesto G, and Hofer, Hans Werner. 2005. "Processing of the human protocadherin Fat1 and translocation of its cytoplasmic domain to the nucleus". United States. https://doi.org/10.1016/j.yexcr.2005.03.006.
@article{osti_20717618,
title = {Processing of the human protocadherin Fat1 and translocation of its cytoplasmic domain to the nucleus},
author = {Magg, Thomas and Schreiner, Dietmar and Solis, Gonzalo P and Bade, Ernesto G and Hofer, Hans Werner},
abstractNote = {The giant protein hFat1, a member of the cadherin superfamily, has been proposed to play roles in cerebral development, glomerular slit formation, and also to act as a tumor suppressor, but its mechanisms of action have not been elucidated. To examine functions of the transmembrane and cytoplasmic domains, they were expressed in HEK293 and HeLa cells as chimeric proteins in fusion with EGFP and extracellular domains derived from E-cadherin. Proteins comprising the transmembrane domain localized to the membrane fraction. Deletion of this domain resulted in a predominantly nuclear localization of the cytoplasmic segment of hFat1. Nuclear localization was largely reduced by deletion of a presumed juxta-membrane NLS. Fusion proteins located in the plasma membrane underwent proteolytic processing. In a first proteolytic step, only the extracellular domain was cleaved off. In another step, the cleavage product was released to the cytosol and was also found in a low speed pellet fraction, in accordance with the nuclear localization of the cytoplasmic domain of hFat1.},
doi = {10.1016/j.yexcr.2005.03.006},
url = {https://www.osti.gov/biblio/20717618}, journal = {Experimental Cell Research},
issn = {0014-4827},
number = 1,
volume = 307,
place = {United States},
year = {Fri Jul 01 00:00:00 EDT 2005},
month = {Fri Jul 01 00:00:00 EDT 2005}
}