ADR1 interacts with a down-stream positive element to activate PS1 transcription.
We have identified downstream promoter sequence of the PS1 gene that may be regulated by novel transcription factors. 3' deletion from +178 to +165 had no effect on PS1 transcription. 3' deletion from +178 to +140 decreased promoter activity by 50%. Further 3' deletion from +178 to +114 decreased promoter activity by 80%. Therefore, a crucial element controlling over 80% of the promoter activity in SK-N-SH cell line is located between +114 and +165. Electrophoretic mobility shift assays suggested that zinc finger proteins Sp1 and ADR1 interacted with the PS1 promoter sequence (+114 to +140) and promoter region (+140 to +165) respectively. A three base pair substitution within the core sequence (GGCGGGGA to GGCGactA) of the ADR1 consensus in the element (+140 to +165) that abolished ADR1-DNA interaction, reduced PS1 transcription by 50%. The substitution mutation in the sequence (+114 to +140) that abolished Sp1-DNA interaction had no effect on PS1 expression. These data suggest that a novel mammalian trans-activator protein ADR1 binds to the downstream element (+140 to +165) to activate PS1 transcription.
Das
Hriday K
HK
Department of Pharmacology and Neuroscience, University of North Texas Health Science Center at Fort Worth, Fort Worth, TX 76107, USA. hdas@hsc.unt.edu
Baez
Myrna L
ML
D000544:Alzheimer Disease / Q000235:genetics*; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics*; D001932:Brain Neoplasms; D027201:Cationic Amino Acid Transporter 1 / Q000235:genetics; D045744:Cell Line, Tumor; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D009447:Neuroblastoma; D016133:Polymerase Chain Reaction; D053764:Presenilin-1 / Q000235:genetics*; D011401:Promoter Regions, Genetic; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
C074682:ADR1 protein, S cerevisiae; D027201:Cationic Amino Acid Transporter 1; D017931:DNA Primers; D004268:DNA-Binding Proteins; D053764:Presenilin-1; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D053829:Amyloid Precursor Protein Secretases