Identification of a novel transcription factor, GAGATA-binding protein, involved in androgen-mediated expression of prostate-specific antigen

Chihuei Wang, Fan Yeung, Po Chun Liu, Ricardo M. Attar, Jieping Geng, Leland W.K. Chung, Marco Gottardis, Chinghai Kao

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Prostate-specific antigen (PSA) is the most valuable marker for the evaluation of prostate cancer progression. The expression of PSA is controlled by androgen receptor (AR) through its binding to androgen-response elements (AREs). Several AREs have been identified within the 5.8-kb PSA promoter. The main activity of this 5.8-kb PSA promoter resides in a 455-bp enhancer core region located about 4 kb upstream of the TATA box. Our study suggests that in addition to the four AREs identified in the PSA enhancer core, another regulatory element (GAGATA), which is located at the region designated PSA3.1, also contributes to transcriptional regulation by androgens. Furthermore, electrophoretic mobility shift assay revealed that a putative transcriptional factor bound the GAGATA sequence in the PSA-producing prostate cancer cell. Further studies demonstrated that GAGATA factor preferentially bound the (G/C)(A/C/T)GATA sequence. The replacement of ATA with GGG in the GAGATA sequence completely eliminated the androgen-mediated transcriptional activity of the enhancer core. By using DNA-coupled magnetic beads and the Southwestern method, a 56-60-kDa protein was identified as the putative GAGATA binding factor. EMSA and Western blotting assay suggested that AR is not involved in androgen-mediated activation through PSA3.1. Therefore, we propose that binding of the GAGATA binding factor and AR to GAGATA and AREs, respectively, of the PSA enhancer core are required for the maximum transcriptional response to androgens.

Original languageEnglish (US)
Pages (from-to)32423-32430
Number of pages8
JournalJournal of Biological Chemistry
Volume278
Issue number34
DOIs
StatePublished - Aug 22 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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