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 i...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
1998-02-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520338876 |
| _version_ | 1818607458623422464 |
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| author | William S. Mohan Zhang-Qun Chen Xia Zhang Kamel Khalili Tasuku Honjo Roger G. Deeley Shui-Pang Tam |
| author_facet | William S. Mohan Zhang-Qun Chen Xia Zhang Kamel Khalili Tasuku Honjo Roger G. Deeley Shui-Pang Tam |
| author_sort | William S. Mohan |
| collection | DOAJ |
| description | 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 (HSμBP2). It is also related to glial factor-1 (GF1), an incomplete version of HSμBP2 lacking the first 494 and the last 128 amino acids. Gel mobility shift assays demonstrated that HSμBP2 binds apoA-I DRE oligomers and forms a specific protein–DNA complex. Northern blot analysis showed that HSμBP2 mRNA is expressed at various levels in a wide range of human tissues. Transient cotransfection experiments performed in HepG2 cells demonstrated that overexpression of HSμBP2 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 HSμBP2 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., Z-Q. Chen, X. Zhang, K. Khalili, T. Honjo, R. G. Deeley, and S-P. Tam. Human S mu binding protein-2 binds to the drug response element and transactivates the human apoA-I promoter: role of gemfibrozil. |
| first_indexed | 2024-12-16T14:27:04Z |
| format | Article |
| id | doaj.art-e0763377719a4b28a05b5d3bc5a180a3 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-16T14:27:04Z |
| publishDate | 1998-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-e0763377719a4b28a05b5d3bc5a180a32022-12-21T22:28:21ZengElsevierJournal of Lipid Research0022-22751998-02-01392255267Human S mu binding protein-2 binds to the drug response element and transactivates the human apoA-I promoter: role of gemfibrozilWilliam S. Mohan0Zhang-Qun Chen1Xia Zhang2Kamel Khalili3Tasuku Honjo4Roger G. Deeley5Shui-Pang Tam6Department of Biochemistry, Queen's University, Kingston, Ontario, Canada K7L 3N6Department of Biochemistry, Queen's University, Kingston, Ontario, Canada K7L 3N6Department of Biochemistry, Queen's University, Kingston, Ontario, Canada K7L 3N6Department of Biochemistry and Molecular Biology, Jefferson Institute of Molecular Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107-6799Department of Medical Chemistry, Kyoto University Faculty of Medicine, Centre for Molecular Biology and Genetics, Sakyo-ku, 606-01, JapanDepartment of Biochemistry, Queen's University, Kingston, Ontario, Canada K7L 3N6To whom correspondence should be addressed.; Department of Biochemistry, Queen's University, Kingston, Ontario, Canada K7L 3N6Previously, 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 (HSμBP2). It is also related to glial factor-1 (GF1), an incomplete version of HSμBP2 lacking the first 494 and the last 128 amino acids. Gel mobility shift assays demonstrated that HSμBP2 binds apoA-I DRE oligomers and forms a specific protein–DNA complex. Northern blot analysis showed that HSμBP2 mRNA is expressed at various levels in a wide range of human tissues. Transient cotransfection experiments performed in HepG2 cells demonstrated that overexpression of HSμBP2 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 HSμBP2 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., Z-Q. Chen, X. Zhang, K. Khalili, T. Honjo, R. G. Deeley, and S-P. Tam. Human S mu binding protein-2 binds to the drug response element and transactivates the human apoA-I promoter: role of gemfibrozil.http://www.sciencedirect.com/science/article/pii/S0022227520338876apolipoprotein A-Igemfibrozilgene expressionregulatory sequencetranscription factor |
| spellingShingle | William S. Mohan Zhang-Qun Chen Xia Zhang Kamel Khalili Tasuku Honjo Roger G. Deeley Shui-Pang Tam Human S mu binding protein-2 binds to the drug response element and transactivates the human apoA-I promoter: role of gemfibrozil Journal of Lipid Research apolipoprotein A-I gemfibrozil gene expression regulatory sequence transcription factor |
| title | Human S mu binding protein-2 binds to the drug response element and transactivates the human apoA-I promoter: role of gemfibrozil |
| title_full | Human S mu binding protein-2 binds to the drug response element and transactivates the human apoA-I promoter: role of gemfibrozil |
| title_fullStr | Human S mu binding protein-2 binds to the drug response element and transactivates the human apoA-I promoter: role of gemfibrozil |
| title_full_unstemmed | Human S mu binding protein-2 binds to the drug response element and transactivates the human apoA-I promoter: role of gemfibrozil |
| title_short | Human S mu binding protein-2 binds to the drug response element and transactivates the human apoA-I promoter: role of gemfibrozil |
| title_sort | human s mu binding protein 2 binds to the drug response element and transactivates the human apoa i promoter role of gemfibrozil |
| topic | apolipoprotein A-I gemfibrozil gene expression regulatory sequence transcription factor |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520338876 |
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