Sterol-independent, sterol response element-dependent, regulation of low density lipoprotein receptor gene expression
Stimulation with phorbol 12-myristate 13-acetate (PMA) and the calcium ionophore ionomycin increased native low density lipoprotein (LDL) receptor gene expression in the human leukemic T cell line Jurkat when cells were cultured in the absence of sterols and also increased nuclear accumulation of st...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Elsevier
1998-08-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520321945 |
| _version_ | 1818601224162770944 |
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| author | Robert S.J. Makar Peter E. Lipsky Jennifer A. Cuthbert |
| author_facet | Robert S.J. Makar Peter E. Lipsky Jennifer A. Cuthbert |
| author_sort | Robert S.J. Makar |
| collection | DOAJ |
| description | Stimulation with phorbol 12-myristate 13-acetate (PMA) and the calcium ionophore ionomycin increased native low density lipoprotein (LDL) receptor gene expression in the human leukemic T cell line Jurkat when cells were cultured in the absence of sterols and also increased nuclear accumulation of sterol regulatory element binding protein (SREBP)-1. PMA and ionomycin likewise increased LDL receptor mRNA levels when cells were cultured in the presence of suppressive concentrations of sterols, when neither SREBP-1 nor SREBP-2 was detectable in the nucleus. These findings indicated that mitogen-induced up-regulation of the LDL receptor gene could be independent of sterol-regulated transcription factors. The involvement of sterol regulatory element (SRE)-1 was analyzed by transfection of LDL receptor promoter constructs. Promoter fragments of either the 5′ 1472 or 142 base pairs induced reporter gene expression after mitogenic stimulation when cells were cultured in the absence or presence of sterols. Mutation of the SRE-1 sequence in either construct abolished sterol-mediated regulation of transcription. However, mutation of the SRE-1 sequence in the 1472 base pair promoter fragment did not alter mitogenic induction of transcription, whereas mutation of SRE-1 in the 142 base pair promoter fragment completely prevented up-regulation of transcription. Taken together, these results demonstrate that the LDL receptor promoter contains at least one 5′ SRE-independent as well as an SRE-dependent response element. Furthermore, the data suggest that the SRE-dependent response may not involve the action of either SREBP-1 or –2. Thus, mitogen-induced transcription of the LDL receptor promoter is regulated by diverse sterol-independent mechanisms.—Makar, R. S. J., P. E. Lipsky, and J. A. Cuthbert. Sterol-independent, sterol response element-dependent, regulation of low density lipoprotein receptor gene expression. |
| first_indexed | 2024-12-16T12:47:59Z |
| format | Article |
| id | doaj.art-e5e1977c775f4439ac096e98a15f54cc |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-16T12:47:59Z |
| publishDate | 1998-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-e5e1977c775f4439ac096e98a15f54cc2022-12-21T22:31:15ZengElsevierJournal of Lipid Research0022-22751998-08-0139816471654Sterol-independent, sterol response element-dependent, regulation of low density lipoprotein receptor gene expressionRobert S.J. Makar0Peter E. Lipsky1Jennifer A. Cuthbert2Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75235-9151Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75235-9151To whom correspondence should be addressed.; Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75235-9151Stimulation with phorbol 12-myristate 13-acetate (PMA) and the calcium ionophore ionomycin increased native low density lipoprotein (LDL) receptor gene expression in the human leukemic T cell line Jurkat when cells were cultured in the absence of sterols and also increased nuclear accumulation of sterol regulatory element binding protein (SREBP)-1. PMA and ionomycin likewise increased LDL receptor mRNA levels when cells were cultured in the presence of suppressive concentrations of sterols, when neither SREBP-1 nor SREBP-2 was detectable in the nucleus. These findings indicated that mitogen-induced up-regulation of the LDL receptor gene could be independent of sterol-regulated transcription factors. The involvement of sterol regulatory element (SRE)-1 was analyzed by transfection of LDL receptor promoter constructs. Promoter fragments of either the 5′ 1472 or 142 base pairs induced reporter gene expression after mitogenic stimulation when cells were cultured in the absence or presence of sterols. Mutation of the SRE-1 sequence in either construct abolished sterol-mediated regulation of transcription. However, mutation of the SRE-1 sequence in the 1472 base pair promoter fragment did not alter mitogenic induction of transcription, whereas mutation of SRE-1 in the 142 base pair promoter fragment completely prevented up-regulation of transcription. Taken together, these results demonstrate that the LDL receptor promoter contains at least one 5′ SRE-independent as well as an SRE-dependent response element. Furthermore, the data suggest that the SRE-dependent response may not involve the action of either SREBP-1 or –2. Thus, mitogen-induced transcription of the LDL receptor promoter is regulated by diverse sterol-independent mechanisms.—Makar, R. S. J., P. E. Lipsky, and J. A. Cuthbert. Sterol-independent, sterol response element-dependent, regulation of low density lipoprotein receptor gene expression.http://www.sciencedirect.com/science/article/pii/S0022227520321945mitogenic activationJurkat cellsphorbol esterintracellular calciumtranscription factors |
| spellingShingle | Robert S.J. Makar Peter E. Lipsky Jennifer A. Cuthbert Sterol-independent, sterol response element-dependent, regulation of low density lipoprotein receptor gene expression Journal of Lipid Research mitogenic activation Jurkat cells phorbol ester intracellular calcium transcription factors |
| title | Sterol-independent, sterol response element-dependent, regulation of low density lipoprotein receptor gene expression |
| title_full | Sterol-independent, sterol response element-dependent, regulation of low density lipoprotein receptor gene expression |
| title_fullStr | Sterol-independent, sterol response element-dependent, regulation of low density lipoprotein receptor gene expression |
| title_full_unstemmed | Sterol-independent, sterol response element-dependent, regulation of low density lipoprotein receptor gene expression |
| title_short | Sterol-independent, sterol response element-dependent, regulation of low density lipoprotein receptor gene expression |
| title_sort | sterol independent sterol response element dependent regulation of low density lipoprotein receptor gene expression |
| topic | mitogenic activation Jurkat cells phorbol ester intracellular calcium transcription factors |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520321945 |
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