PMID- 8887630 OWN - NLM STAT- MEDLINE DCOM- 19961216 LR - 20210526 IS - 0270-7306 (Print) IS - 1098-5549 (Electronic) IS - 0270-7306 (Linking) VI - 16 IP - 11 DP - 1996 Nov TI - Transcriptional activation of the human epidermal growth factor receptor promoter by human p53. PG - 6009-19 AB - The human epidermal growth factor receptor (EGFR) promoter is activated by both wild-type and tumor-derived mutant p53. In this communication, we demonstrate that EGFR promoter sequence requirements for transactivation by wild-type and mutant p53 are different. Transient-expression assays with EGFR promoter deletions identified a wild-type human p53 response element, 5'-AGCTAGACGTCCGGGCAGCCCCCGGCG -3', from positions --265 to --239. Electrophoretic mobility shift analysis and DNase I footprinting assays indicated that wild-type p53 binds sequence specifically to the response element. Using circularly permuted DNA fragments containing the p53-binding site, we show that wild-type p53 binding induces DNA bending at this site. We further show that the EGFR promoter is also activated by tumor-derived p53 mutants p53-143A, p53-175H, p53-248W, p53-273H, and p53-281G. However, the transactivation by mutant p53 does not require the wild-type p53-binding site. The minimal EGFR promoter from positions --104 to --20 which does not contain the wild-type p53-binding site is transactivated by the p53 mutants but not by the wild-type protein, showing a difference in the mechanism of transactivation by wild-type and mutant p53. Transactivation of the EGFR promoter by p53 may represent a novel mechanism of cell growth regulation. FAU - Ludes-Meyers, J H AU - Ludes-Meyers JH AD - Department of Microbiology, University of Texas Health Science Center at San Antonio, 78284, USA. FAU - Subler, M A AU - Subler MA FAU - Shivakumar, C V AU - Shivakumar CV FAU - Munoz, R M AU - Munoz RM FAU - Jiang, P AU - Jiang P FAU - Bigger, J E AU - Bigger JE FAU - Brown, D R AU - Brown DR FAU - Deb, S P AU - Deb SP FAU - Deb, S AU - Deb S LA - eng GR - AI31498-02/AI/NIAID NIH HHS/United States GR - CA70712/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Mol Cell Biol JT - Molecular and cellular biology JID - 8109087 RN - 0 (Recombinant Proteins) RN - 0 (Tumor Suppressor Protein p53) RN - EC 2.3.1.28 (Chloramphenicol O-Acetyltransferase) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Amino Acid Sequence MH - Base Composition MH - Base Sequence MH - Binding Sites MH - Chloramphenicol O-Acetyltransferase/biosynthesis MH - ErbB Receptors/*biosynthesis/*genetics MH - Humans MH - Molecular Sequence Data MH - Polymerase Chain Reaction MH - *Promoter Regions, Genetic MH - Recombinant Proteins/biosynthesis MH - Regulatory Sequences, Nucleic Acid MH - Restriction Mapping MH - Sequence Deletion MH - TATA Box MH - *Transcriptional Activation MH - Tumor Suppressor Protein p53/*metabolism PMC - PMC231603 EDAT- 1996/11/01 00:00 MHDA- 1996/11/01 00:01 PMCR- 1996/11/01 CRDT- 1996/11/01 00:00 PHST- 1996/11/01 00:00 [pubmed] PHST- 1996/11/01 00:01 [medline] PHST- 1996/11/01 00:00 [entrez] PHST- 1996/11/01 00:00 [pmc-release] AID - 10.1128/MCB.16.11.6009 [doi] PST - ppublish SO - Mol Cell Biol. 1996 Nov;16(11):6009-19. doi: 10.1128/MCB.16.11.6009.