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

The Journal of Biological Chemistry
Chihuei WangChinghai Kao

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 as...Continue Reading

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Citations

Jun 6, 2012·Molecular and Cellular Biology·Hongbo WangChunhong Yan
May 12, 2009·Journal of Biotechnology·Noémie Manuelle Dorval CourchesneChristopher Q Lan
Aug 13, 2004·European Urology·Michèle Algarté-GéninPierre Costa
Apr 25, 2006·Biochemical and Biophysical Research Communications·Po-Jen ChenMing-Shi Chang
Apr 15, 2004·Endocrine Reviews·Cynthia A Heinlein, Chawnshang Chang
Jun 21, 2006·Molecular and Cellular Biochemistry·Chihuei WangGwo-Jaw Wang
Mar 13, 2021·Carcinogenesis·Timothy O AdekoyaRicardo M Richardson

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