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Title: Nuclear localization of coactivator RAC3 is mediated by a bipartite NLS and importin {alpha}3

Abstract

The nuclear receptor coactivator RAC3 (also known as SRC-3/ACTR/AIB1/p/CIP/TRAM-1) belongs to the p160 coactivator family, which are involved in several physiological processes and diseases. Here we have investigated how RAC3 is translocated into the nucleus and show that it is mediated through a bipartite NLS and importin {alpha}3. This bipartite NLS is located within the conserved bHLH domain, and its mutation abolished nuclear localization. The NLS is also sufficient to cause nuclear import of EGFP, and the activity requires basic amino acids within the NLS. RAC3 binds strongly to importin {alpha}3, which also depends on the basic amino acids. Functionally, RAC3 cytoplasmic mutant loses its ability to enhance transcription, suggesting that nuclear localization is essential for coactivator function. Together, these results reveal a previous unknown mechanism for nuclear translocation of p160 coactivators and a critical function of the conserved bHLH within the coactivator.

Authors:
 [1];  [1];  [1]
  1. Department of Pharmacology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, NJ (United States)
Publication Date:
OSTI Identifier:
20854454
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 348; Journal Issue: 1; Other Information: DOI: 10.1016/j.bbrc.2006.06.163; PII: S0006-291X(06)01479-3; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; AMINO ACIDS; CELL NUCLEI; DISEASES; MUTANTS; MUTATIONS; RECEPTORS; TRANSCRIPTION; TRANSLOCATION

Citation Formats

Yeung, Percy Luk, Zhang, Aihua, and Chen, J Don. Nuclear localization of coactivator RAC3 is mediated by a bipartite NLS and importin {alpha}3. United States: N. p., 2006. Web. doi:10.1016/j.bbrc.2006.06.163.
Yeung, Percy Luk, Zhang, Aihua, & Chen, J Don. Nuclear localization of coactivator RAC3 is mediated by a bipartite NLS and importin {alpha}3. United States. https://doi.org/10.1016/j.bbrc.2006.06.163
Yeung, Percy Luk, Zhang, Aihua, and Chen, J Don. 2006. "Nuclear localization of coactivator RAC3 is mediated by a bipartite NLS and importin {alpha}3". United States. https://doi.org/10.1016/j.bbrc.2006.06.163.
@article{osti_20854454,
title = {Nuclear localization of coactivator RAC3 is mediated by a bipartite NLS and importin {alpha}3},
author = {Yeung, Percy Luk and Zhang, Aihua and Chen, J Don},
abstractNote = {The nuclear receptor coactivator RAC3 (also known as SRC-3/ACTR/AIB1/p/CIP/TRAM-1) belongs to the p160 coactivator family, which are involved in several physiological processes and diseases. Here we have investigated how RAC3 is translocated into the nucleus and show that it is mediated through a bipartite NLS and importin {alpha}3. This bipartite NLS is located within the conserved bHLH domain, and its mutation abolished nuclear localization. The NLS is also sufficient to cause nuclear import of EGFP, and the activity requires basic amino acids within the NLS. RAC3 binds strongly to importin {alpha}3, which also depends on the basic amino acids. Functionally, RAC3 cytoplasmic mutant loses its ability to enhance transcription, suggesting that nuclear localization is essential for coactivator function. Together, these results reveal a previous unknown mechanism for nuclear translocation of p160 coactivators and a critical function of the conserved bHLH within the coactivator.},
doi = {10.1016/j.bbrc.2006.06.163},
url = {https://www.osti.gov/biblio/20854454}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 1,
volume = 348,
place = {United States},
year = {Fri Sep 15 00:00:00 EDT 2006},
month = {Fri Sep 15 00:00:00 EDT 2006}
}