Cloning and characterization of the human BAG-1 gene promoter: Upregulation by tumor-derived p53 mutants

Xiaolong Yang, Alan Pater, Shou Ching Tang

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

BAG-1 is an anti-apoptotic protein that interacts with Bcl-2, Bcl-X(L), Hsp70/Hsc70, Raf-1 and numerous hormone or growth factor receptors. Recently, BAG-1 has been found to be overexpressed in a variety of human cancer cell lines and some tumors. However, the molecular mechanism of BAG-1 upregulation is still unclear. In this study, we cloned 0.9 kb of human genomic DNA, BGEV, 5' flanking the BAG-1 open reading frame. BGEV subcloned into a promoterless luciferase reporter vector conferred high promoter activity in various human cancer cell lines. Deletion analysis of this sequence localized the region of maximal BAG-1 promoter activity from nucleotide positions -353 to -54, upstream of the first start codon CTG. Sequence analysis of the BAG-1 promoter region showed the absence of a TATA box but identified a CCAAT box, several GC boxes, a CpG island and several transcriptional factor binding sites, which may be important in the regulation of BAG-1 transcription. Most importantly, functional characterization of the BAG-1 promoter in vitro demonstrated that gain-of-function p53 mutants derived from human tumors upregulated the transcription of BAG-1 RNA and the expression of a reporter gene from the BAG-1 promoter. These results indicated that we have isolated the functional constitutive BAG-1 promoter. Furthermore, the data suggested that overexpression of BAG-1 in some tumors may be due to upregulation of the human BAG-1 promoter by mutant p53.

Original languageEnglish (US)
Pages (from-to)4546-4553
Number of pages8
JournalOncogene
Volume18
Issue number32
DOIs
StatePublished - Aug 12 1999

Keywords

  • BAG-1
  • Mutant p53
  • Promoter
  • Transactivation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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