Transcriptional regulation of human 3'-phosphoadenosine 5'-phosphosulfate synthase 1.
Sulfonation, which is essential for normal growth, development and maintenance of the internal milieu, requires the universal sulfonate donor molecule 3'-phosphoadenosine 5'-phosphosulfate (PAPS) produced from ATP and inorganic sulfate by two bifunctional PAPS synthase isozymes. The gene for PAPS synthase 1 containing neither a TATA nor a CCAAT box was found to be under the influence of the Sp1 family of transcription factors. Multiple GC/GT boxes are present in the proximal promoter region and deletion analysis implicated their involvement in transcription, a finding supported by mutational analysis of specific GC/GT boxes. Nuclear extract of SW13 cells, which highly express PAPS synthase 1, contains proteins that bind to probes possessing specific GC/GT boxes; furthermore, the presence of Sp1, Sp2, and Sp3 proteins in nuclear extracts was confirmed by supershift analysis. Cotransfection experiments using SL2 cells yielded additional support for the involvement of Sp1 in transcriptional regulation of the PAPS synthase 1 gene; the involvement of Sp2 and/or Sp3 is presently unclear.
Shimizu
C
C
Section on Steroid Regulation, Endocrinology and Reproduction Research Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA.
Fuda
H
H
Lee
Y C
YC
Strott
C A
CA
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology; D004591:Electrophoresis, Polyacrylamide Gel; D017930:Genes, Reporter; D006801:Humans; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D020218:Response Elements; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000502:physiology; D051705:Sp3 Transcription Factor; D013430:Sulfate Adenylyltransferase / Q000096:biosynthesis / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology; D014158:Transcription, Genetic; D014162:Transfection
D004268:DNA-Binding Proteins; D009097:Multienzyme Complexes; C497121:SP3 protein, human; D016329:Sp1 Transcription Factor; D014157:Transcription Factors; D051705:Sp3 Transcription Factor; C022322:PAPS synthetase; D013430:Sulfate Adenylyltransferase