Expression of the human TPT1 gene coding for translationally controlled tumor protein (TCTP) is regulated by CREB transcription factors.
Re-evaluation of genomic and cDNA data revealed that the human TPT1 gene coding for the translationally controlled tumor protein (TCTP) consists of at least 4211 base pairs. It is transcribed into two transcripts of about 0.8 and 1.2 kb, which contain the same coding region and 5'-UTR, but differ in the length of 3'-UTRs by the use of alternative polyadenylation signals. 459 bp promoter sequences were analyzed by theoretical evaluation, reporter-gene assays, gelshift and footprinting experiments to search for transcription factor binding sites. The promoter contains two highly conserved CRE sites between -50 and -89 in close vicinity to a TATA-box at -30. Supershift assays identified CREB I and Fra II of the CREB/ATF1/AP1 family as factors interacting with the CRE/AP1 site. A 3-5-fold stimulation of TCTP synthesis by forskolin and phorbolester in T24 cells and promoter-reporter experiments using CRE-deletion constructs suggested a transcriptional control by cAMP signaling via phosphorylation dependent activation of CRE/CREB interaction.
Andree
Holger
H
Charité, Universitätsmedizin Berlin, Institut für Vegetative Physiologie, Tucholskystr. 2, 10117 Berlin, Germany.
Thiele
Holger
H
Fähling
Michael
M
Schmidt
Irina
I
Thiele
Bernd-Joachim
BJ
D024506:5' Flanking Region / Q000235:genetics; D000818:Animals; D001665:Binding Sites; D014408:Biomarkers, Tumor; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D018983:DNA Footprinting / Q000379:methods; D004268:DNA-Binding Proteins / Q000378:metabolism; D004285:Dogs; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011817:Rabbits; D051381:Rats; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D000090324:Tumor Protein, Translationally-Controlled 1
D014408:Biomarkers, Tumor; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010703:Phorbol Esters; C000715647:TPT1 protein, human; C000715648:Tpt1 protein, mouse; C000715649:Tpt1 protein, rat; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D000090324:Tumor Protein, Translationally-Controlled 1; D005576:Colforsin; D000242:Cyclic AMP