Document Detail

Sterol-independent, sterol response element-dependent, regulation of low density lipoprotein receptor gene expression.
MedLine Citation:
PMID:  9717725     Owner:  NLM     Status:  MEDLINE    
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.
R S Makar; P E Lipsky; J A Cuthbert
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of lipid research     Volume:  39     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  1998 Aug 
Date Detail:
Created Date:  1998-11-16     Completed Date:  1998-11-16     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1647-54     Citation Subset:  IM    
Department of Internal Medicine, The University of Texas Southwestern Medical Center at Dallas, 75235-9151, USA.
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MeSH Terms
Base Sequence
CCAAT-Enhancer-Binding Proteins*
Chloramphenicol O-Acetyltransferase / biosynthesis,  genetics
DNA / genetics
DNA-Binding Proteins / metabolism
Gene Expression Regulation / drug effects
Ionomycin / pharmacology
Ionophores / pharmacology
Jurkat Cells
Nuclear Proteins / metabolism
Promoter Regions, Genetic
RNA, Messenger / genetics,  metabolism
Receptors, LDL / genetics*,  metabolism*
Sterol Regulatory Element Binding Protein 1
Sterol Regulatory Element Binding Protein 2
Sterols / metabolism*
Tetradecanoylphorbol Acetate / pharmacology
Transcription Factors / metabolism
Grant Support
Reg. No./Substance:
0/CCAAT-Enhancer-Binding Proteins; 0/DNA-Binding Proteins; 0/Ionophores; 0/Nuclear Proteins; 0/RNA, Messenger; 0/Receptors, LDL; 0/SREBF1 protein, human; 0/SREBF2 protein, human; 0/Sterol Regulatory Element Binding Protein 1; 0/Sterol Regulatory Element Binding Protein 2; 0/Sterols; 0/Transcription Factors; 16561-29-8/Tetradecanoylphorbol Acetate; 56092-81-0/Ionomycin; 9007-49-2/DNA; EC O-Acetyltransferase

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