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Subcellular localization of ankyrin repeats cofactor‐1 regulates its corepressor activity
Author(s) -
Zhang Aihua,
Li ChiaWei,
Tsai ShihChieh,
Chen J. Don
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21251
Subject(s) - corepressor , nuclear localization sequence , subcellular localization , microbiology and biotechnology , nuclear export signal , nuclear receptor , transcription factor , ankyrin repeat , nuclear transport , biology , nuclear protein , transcription (linguistics) , cell nucleus , cytoplasm , biochemistry , gene , linguistics , philosophy
The ankyrin repeats cofactor‐1 (ANCO‐1) was recently identified as a novel nuclear receptor corepressor that regulates receptor‐mediated transcription through interactions with p160 coactivators and histone deacetylases. Interestingly, exogenously expressed ANCO‐1 is localized at distinct subnuclear domains. The relevance of these subnuclear domains and the mechanisms of nucleocytoplasmic translocation of ANCO‐1 have not been determined. We report here the identification of an N‐terminal signaling motif that is essential for both nuclear/subnuclear localization and transcription corepressor function of ANCO‐1. This N‐terminal motif at residues 80–86 of ANCO‐1 constitutes a classical nuclear localization signal (NLS1). Disruption of NLS1 causes complete cytoplasmic accumulation of the full‐length ANCO‐1, and abolishes its corepressor function on receptor‐mediated transcription. A second NLS (NLS2) is found at the C‐terminal residues 2384–2390; however, its disruption abolishes only nuclear localization of isolated C‐terminal fragments. We also identify a leucine‐rich nuclear export signal (NES) at residues 2415–2424 of ANCO‐1, and show that both the NLSs and NES sequences are capable of mediating nuclear import and export of heterologous protein, respectively. In addition, attachment of the NES sequence to a transcription factor impairs its activation function. These results suggest that ANCO‐1 subnuclear localization is regulated by both nuclear import and export signals, and that proper subcellular localization of ANCO‐1 is essential for its corepressor function. J. Cell. Biochem. 101:1301–1315, 2007. © 2007 Wiley‐Liss, Inc.