Nuclear receptor interaction protein, a coactivator of androgen receptors (AR), is regulated by AR and Sp1 to feed forward and activate its own gene expression through AR protein stability
Journal
Nucleic Acids Research
Journal Volume
36
Journal Issue
1
Pages
51-66
Date Issued
2008
Author(s)
Abstract
Previously, we found a novel gene, nuclear receptor interaction protein (NRIP), a transcription cofactor that can enhance an AR-driven PSA promoter activity in a ligand-dependent manner in prostate cancer cells. Here, we investigated NRIP regulation. We cloned a 413-bp fragment from the transcription initiation site of the NRIP gene that had strong promoter activity, was TATA-less and GC-rich, and, based on DNA sequences, contained one androgen response element (ARE) and three Sp1-binding sites (Sp1-1, Sp1-2, Sp1-3). Transient promoter luciferase assays, chromatin immunoprecipitation and small RNA interference analyses mapped ARE and Sp1-2-binding sites involved in NRIP promoter activation, implying that NRIP is a target gene for AR or Sp1. AR associates with the NRIP promoter through ARE and indirectly through Sp1-binding site via AR-Sp1 complex formation. Thus both ARE and Sp1-binding site within the NRIP promoter can respond to androgen induction. More intriguingly, NRIP plays a feed-forward role enhancing AR-driven NRIP promoter activity via NRIP forming a complex with AR to protect AR protein from proteasome degradation. This is the first demonstration that NRIP is a novel AR-target gene and that NRIP expression feeds forward and activates its own expression through AR protein stability. ? 2007 The Author(s).
SDGs
Other Subjects
androgen receptor; cytosine; DNA; guanine; luciferase; nuclear receptor interaction protein; prostate specific antigen; proteasome; transcription factor; transcription factor Sp1; unclassified drug; androgen responsive element; article; binding site; chromatin immunoprecipitation; complex formation; controlled study; DNA sequence; GC rich sequence; gene expression regulation; gene targeting; hormone responsive element; human; human cell; molecular cloning; nucleotide sequence; priority journal; promoter region; prostate cancer; protein degradation; protein stability; regulatory mechanism; RNA interference; TATA box; transcription initiation site; Amino Acid Sequence; Animals; Base Sequence; Binding Sites; Cell Line; Cell Line, Tumor; Humans; Male; Molecular Sequence Data; Nuclear Proteins; Promoter Regions (Genetics); Prostatic Neoplasms; Receptors, Androgen; RNA, Messenger; Sp1 Transcription Factor; Trans-Activation (Genetics); Up-Regulation
Type
journal article