Human S mu binding protein-2 binds to the drug response element and transactivates the human apoA-I promoter: role of gemfibrozil.
Previously, we demonstrated that protein-DNA interactions at the drug response element (DRE) in the human apoA-I promoter were important for the induction of apoA-I gene expression by gemfibrozil. We now report the cloning and characterization of a DRE transactivating factor. The cloned protein is identical to the putative helicase and potential transcription factor human S mu binding protein-2 (HSmuBP2). It is also related to glial factor-1 (GF1), an incomplete version of HSmuBP2 lacking the first 494 and the last 128 amino acids. Gel mobility shift assays demonstrated that HSmuBP2 binds apoA-I DRE oligomers and forms a specific protein-DNA complex. Northern blot analysis showed that HSmuBP2 mRNA is expressed at various levels in a wide range of human tissues. Transient cotransfection experiments performed in HepG2 cells demonstrated that overexpression of HSmuBP2 or GF1 induced apoA-I proximal promoter activity by 3-fold and that the apoA-I DRE was necessary for transactivation. Additionally, we demonstrated that transactivation was increased a further 2- to 3-fold by exposing the cells to gemfibrozil. Together these observations indicate that HSmuBP2 acts as a transcription factor that regulates apoA-I gene expression in hepatoma cells and whose activity may be stimulated by gemfibrozil treatment.
Mohan
W S
WS
Department of Biochemistry, Queen's University, Kingston, Ontario, Canada.
Chen
Z Q
ZQ
Zhang
X
X
Khalili
K
K
Honjo
T
T
Deeley
R G
RG
Tam
S P
SP
D016632:Apolipoprotein A-I / Q000235:genetics*; D015152:Blotting, Northern; D006528:Carcinoma, Hepatocellular; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015248:Gemfibrozil / Q000494:pharmacology*; D015870:Gene Expression; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008113:Liver Neoplasms; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D016632:Apolipoprotein A-I; D004268:DNA-Binding Proteins; D000960:Hypolipidemic Agents; C489892:IGHMBP2 protein, human; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D015248:Gemfibrozil