Identification of a novel family of ankyrin repeats containing cofactors for p160 nuclear receptor coactivators.
Members of the p160 nuclear receptor coactivators interact with liganded nuclear receptors to enhance transcription of target genes. Here we identify a novel family of ankyrin repeats containing cofactors (ANCOs) that interact with the p160 coactivators. ANCO-1 binds to the conserved Per-Arnt-Sim (PAS) region of the p160 coactivators. It encodes a large nuclear protein with five ankyrin repeats, and parts of its sequences have been reported as nasopharyngeal carcinoma susceptibility protein and medulloblastoma antigen. Immunofluorescence staining reveals discrete nuclear foci of ANCO-1 that are distinct from known nuclear structures. Intriguingly, ANCO-1 also colocalizes and interacts with histone deacetylases. Transient reporter gene assay shows that ANCO-1 expression inhibits ligand-dependent transactivation by both steroid and nonsteroid nuclear receptors. Taken together, we have identified a novel family of ankyrin repeats containing cofactors that may recruit histone deacetylases to the p160 coactivators/nuclear receptor complex to inhibit ligand-dependent transactivation.
Zhang
Aihua
A
Department of Pharmacology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854-5635, USA.
Yeung
Percy Luk
PL
Li
Chia-Wei
CW
Tsai
Shih-Chieh
SC
Dinh
Gia Khanh
GK
Wu
Xiaoyang
X
Li
Hui
H
Chen
J Don
JD
D000595:Amino Acid Sequence; D017487:Ankyrins / Q000737:chemistry*; D001665:Binding Sites; D002467:Cell Nucleus / Q000737:chemistry; D017124:Conserved Sequence; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D005982:Glutathione Transferase / Q000235:genetics; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D056920:Nuclear Receptor Coactivator 1; D051958:Nuclear Receptor Coactivator 2; D056921:Nuclear Receptor Coactivator 3; D010446:Peptide Fragments / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D012091:Repetitive Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D016415:Sequence Alignment; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection
C492515:ANKRD11 protein, human; D017487:Ankyrins; C498001:NCOA2 protein, human; D051958:Nuclear Receptor Coactivator 2; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; D056920:Nuclear Receptor Coactivator 1; D056921:Nuclear Receptor Coactivator 3; D005982:Glutathione Transferase; D006655:Histone Deacetylases