Nuclear localization of coactivator RAC3 is mediated by a bipartite NLS and importin α3

Percy Luk Yeung, Aihua Zhang, J. Don Chen

Research output: Contribution to journalArticle

12 Scopus citations

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 α3. 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 α3, 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.

Original languageEnglish (US)
Pages (from-to)13-24
Number of pages12
JournalBiochemical and Biophysical Research Communications
Volume348
Issue number1
DOIs
StatePublished - Sep 15 2006

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Biophysics
  • Biochemistry
  • Cell Biology

Keywords

  • Bipartite NLS
  • Importin α3
  • Nuclear localization
  • Nuclear receptor coactivator
  • RAC3
  • p160

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