PMID- 8086478 OWN - NLM STAT- MEDLINE DCOM- 19941020 LR - 20190610 IS - 0006-3002 (Print) IS - 0006-3002 (Linking) VI - 1219 IP - 1 DP - 1994 Sep 13 TI - Binding of AP-1/CREB proteins and of MDBP to contiguous sites downstream of the human TGF-beta 1 gene. PG - 55-63 AB - Transcription of the human gene encoding transforming growth factor beta 1 (TGF-beta 1), which is a key regulator of cell growth and differentiation, is inducible by phorbol esters. DNA sequences resembling phorbol ester response elements (TREs) are present upstream and downstream of this gene. TREs are recognized by proteins from the AP-1 family of transcription factors. We examined a 16 basepair (bp) sequence downstream of the TGF-beta 1 gene that contains three putative TREs. This sequence had been shown to stimulate reporter gene expression from a downstream location in response to phorbol ester treatment. Electrophoretic mobility shift assays suggest that minor proteins from the related AP-1 and CREB families of transcription factors bind to the overlapping TREs within the 16 bp element. A site beginning at the end of this 16 bp element matches the consensus sequence of a DNA-binding protein called MDBP and was shown to bind to this protein. When the intact MDBP site was present in a reporter gene construct in addition to the TREs, the phorbol ester-induced stimulation of reporter gene expression was no longer observed. This suggests that MDBP can counteract the stimulation of transcription by AP-1/CREB-like proteins binding to this downstream enhancer element. FAU - Asiedu, C K AU - Asiedu CK AD - Department of Biochemistry SL43, Tulane Medical School, New Orleans, LA 70112. FAU - Scotto, L AU - Scotto L FAU - Assoian, R K AU - Assoian RK FAU - Ehrlich, M AU - Ehrlich M LA - eng GR - GM33999/GM/NIGMS NIH HHS/United States GR - HL38884/HL/NHLBI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - Netherlands TA - Biochim Biophys Acta JT - Biochimica et biophysica acta JID - 0217513 RN - 0 (Cyclic AMP Response Element-Binding Protein) RN - 0 (DNA-Binding Proteins) RN - 0 (MBD1 protein, human) RN - 0 (Oligodeoxyribonucleotides) RN - 0 (Proto-Oncogene Proteins c-jun) RN - 0 (Recombinant Fusion Proteins) RN - 0 (Transcription Factors) RN - 0 (Transforming Growth Factor beta) RN - 9007-49-2 (DNA) SB - IM MH - Base Sequence MH - Cyclic AMP Response Element-Binding Protein/classification/*metabolism MH - DNA/*metabolism MH - DNA-Binding Proteins/*metabolism MH - Genes, Reporter MH - Humans MH - Methylation MH - Molecular Sequence Data MH - Oligodeoxyribonucleotides/metabolism MH - Protein Binding MH - Proto-Oncogene Proteins c-jun/classification/*metabolism MH - Recombinant Fusion Proteins/biosynthesis MH - Regulatory Sequences, Nucleic Acid/*genetics MH - Structure-Activity Relationship MH - Transcription Factors MH - Transcription, Genetic MH - Transforming Growth Factor beta/biosynthesis/*genetics MH - Tumor Cells, Cultured EDAT- 1994/09/13 00:00 MHDA- 1994/09/13 00:01 CRDT- 1994/09/13 00:00 PHST- 1994/09/13 00:00 [pubmed] PHST- 1994/09/13 00:01 [medline] PHST- 1994/09/13 00:00 [entrez] AID - 0167-4781(94)90246-1 [pii] AID - 10.1016/0167-4781(94)90246-1 [doi] PST - ppublish SO - Biochim Biophys Acta. 1994 Sep 13;1219(1):55-63. doi: 10.1016/0167-4781(94)90246-1.