Identification of the promoter of the human von Hippel-Lindau disease tumor suppressor gene.
The von Hippel-Lindau (VHL) disease gene is a novel multiple tumor suppressor gene which plays a causal role in the origin of some common cancers including clear cell renal carcinomas and hemangioblastomas of the central nervous system. Here we report the identification of transcription start sites and the promoter of the human VHL gene. The promoter sequence does not contain TATA and CCAAT boxes. Transcription is initiated around a putative SP1 binding site about 60 bp upstream from the first AUG codon in the VHL mRNA. Several putative transcription factor binding sites, notably for nuclear respiratory factor 1 and PAX, were found upstream of the transcription start sites. Promoter-luciferase expression constructs demonstrate, that the promoter is functional when transfected into 293 cells (transformed primary human embryonal kidney cells) and UMRC 6 renal carcinoma cells. Activity is dependent on correct orientation of the promoter. A minimal promoter region of 106 bp was delineated. A set of VHL minigenes, containing the 5' flanking VHL genomic region, was constructed and transfected into UMRC 6 cells. In these cells the level of transcription from the minigenes driven by VHL promoter was comparable with endogenous VHL expression.
Kuzmin
I
I
Laboratory of Immunobiology, NCI-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA.
Duh
F M
FM
Latif
F
F
Geil
L
L
Zbar
B
B
Lerman
M I
MI
D000595:Amino Acid Sequence; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary; D016147:Genes, Tumor Suppressor; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D006623:von Hippel-Lindau Disease / Q000235:genetics*
D018076:DNA, Complementary