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 Citations (Scopus)

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

Fingerprint

Carcinogens
Organism Cloning
Up-Regulation
Genes
Sequence Analysis
Neoplasms
TATA Box
Apoptosis Regulatory Proteins
CpG Islands
Initiator Codon
Growth Factor Receptors
Sequence Deletion
Tumor Cell Line
Luciferases
Reporter Genes
Genetic Promoter Regions
Open Reading Frames
Nucleotides
Binding Sites
Hormones

Keywords

  • BAG-1
  • Mutant p53
  • Promoter
  • Transactivation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Cloning and characterization of the human BAG-1 gene promoter : Upregulation by tumor-derived p53 mutants. / Yang, Xiaolong; Pater, Alan; Tang, Shou-Ching.

In: Oncogene, Vol. 18, No. 32, 12.08.1999, p. 4546-4553.

Research output: Contribution to journalArticle

Yang, Xiaolong ; Pater, Alan ; Tang, Shou-Ching. / Cloning and characterization of the human BAG-1 gene promoter : Upregulation by tumor-derived p53 mutants. In: Oncogene. 1999 ; Vol. 18, No. 32. pp. 4546-4553.
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