| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J Biol Chem, Vol. 274, Issue 35, 24714-24720, August 27, 1999
,,,,
From the § Department of Applied Biological Chemistry,
Graduate School of Agriculture and Life Sciences, The University of
Tokyo, 1-1-1 Yayou, Bunkyo, Tokyo 113-8657, Japan, the
We herein report that mRNA
expression of microsomal triglyceride transfer protein (MTP) and its
protein synthesis decline in response to sterol depletion in HepG2
cells, and we functionally characterized the MTP gene promoter in an
effort to investigate the molecular mechanisms by which MTP gene
transcription is regulated. Luciferase assays using truncated versions
of the reporter gene revealed that the region at Laboratory of Biochemistry and Molecular Biology,
Graduate School of Pharmaceutical Sciences, Osaka University, Suita,
Osaka 565-0871, Japan and the ¶ Department of Biological
Chemistry, Faculty of Pharmaceutical Sciences, Toyama Medical and
Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan
124 to +33 base
pairs of the human promoter contains the elements required for the
suppression of transcription by sterol depletion. Enforced expression
of an active form of sterol regulatory element-binding protein
(SREBP)-1 (amino acids 1-487) or -2 (amino acids 1-481), both of
which are activated under sterol-depleted conditions, is able to mimic
sterol-mediated down-regulation. Either further truncation of the
promoter region or mutation of the putative SREBP-binding sequence
(5'-GCAGCCCAC-3', 124 to 116 base pairs) abolishes the sterol- and
SREBP-dependent transcriptional regulation. Gel mobility
shift assay showed that recombinant SREBP-2-(1-481) is able to bind
the sequence. Enforced expression of a truncated form of SREBP-2 (amino
acids 31-481), which acts as an inhibitor of transcription of the low
density lipoprotein receptor gene because it lacks the transcriptional activation domain, also diminishes the luciferase activity, suggesting that direct binding to the promoter region might be sufficient and that
the mechanism by which SREBPs inhibit MTP gene expression is distinct
from that for the transcriptional stimulation of sterol-regulated genes. Although the SREBP-binding site overlaps a negative
insulin-responsive element, insulin negatively regulates MTP gene
expression even when the amount of the active form of SREBPs is quite
low under the sterol-loaded conditions, indicating that SREBPs only
slightly mediate, if at all, the insulin effects. Overall, we conclude that SREBPs are responsible for regulation of lipoprotein secretion via
their control of MTP gene expression. Moreover, our results describe
for the first time a novel mechanism by which SREBPs negatively
regulate expression of the gene encoding the protein involved in lipid metabolism.
This article has been cited by other articles:
|
|
 |
|
  S. Loeper, S. L. Asa, and S. Ezzat Ikaros Modulates Cholesterol Uptake: A Link between Tumor Suppression and Differentiation Cancer Res., May 15, 2008; 68(10): 3715 - 3723. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Li, M. Naples, H. Song, R. Yuan, F. Ye, S. Shafi, K. Adeli, and D. S. Ng LCAT-null mice develop improved hepatic insulin sensitivity through altered regulation of transcription factors and suppressors of cytokine signaling Am J Physiol Endocrinol Metab, August 1, 2007; 293(2): E587 - E594. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Morral, H. J. Edenberg, S. R. Witting, J. Altomonte, T. Chu, and M. Brown Effects of glucose metabolism on the regulation of genes of fatty acid synthesis and triglyceride secretion in the liver J. Lipid Res., July 1, 2007; 48(7): 1499 - 1510. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kanayama, M. Arito, K. So, S. Hachimura, J. Inoue, and R. Sato Interaction between Sterol Regulatory Element-binding Proteins and Liver Receptor Homolog-1 Reciprocally Suppresses Their Transcriptional Activities J. Biol. Chem., April 6, 2007; 282(14): 10290 - 10298. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Amemiya-Kudo, J. Oka, T. Ide, T. Matsuzaka, H. Sone, T. Yoshikawa, N. Yahagi, S. Ishibashi, J.-i. Osuga, N. Yamada, et al. Sterol Regulatory Element-binding Proteins Activate Insulin Gene Promoter Directly and Indirectly through Synergy with BETA2/E47 J. Biol. Chem., October 14, 2005; 280(41): 34577 - 34589. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Allister, N. M. Borradaile, J. Y. Edwards, and M. W. Huff Inhibition of Microsomal Triglyceride Transfer Protein Expression and Apolipoprotein B100 Secretion by the Citrus Flavonoid Naringenin and by Insulin Involves Activation of the Mitogen-Activated Protein Kinase Pathway in Hepatocytes Diabetes, June 1, 2005; 54(6): 1676 - 1683. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. V. Nerurkar, L. Pearson, J. T. Efird, K. Adeli, A. G. Theriault, and V. R. Nerurkar Microsomal Triglyceride Transfer Protein Gene Expression and ApoB Secretion Are Inhibited by Bitter Melon in HepG2 Cells J. Nutr., April 1, 2005; 135(4): 702 - 706. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Sheena, R. Hertz, J. Nousbeck, I. Berman, J. Magenheim, and J. Bar-Tana Transcriptional regulation of human microsomal triglyceride transfer protein by hepatocyte nuclear factor-4{alpha} J. Lipid Res., February 1, 2005; 46(2): 328 - 341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Jakel, M. Nowak, E. Moitrot, H. Dehondt, D. W. Hum, L. A. Pennacchio, J. Fruchart-Najib, and J.-C. Fruchart The Liver X Receptor Ligand T0901317 Down-regulates APOA5 Gene Expression through Activation of SREBP-1c J. Biol. Chem., October 29, 2004; 279(44): 45462 - 45469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-F. Landrier, C. Thomas, J. Grober, H. Duez, F. Percevault, M. Souidi, C. Linard, B. Staels, and P. Besnard Statin Induction of Liver Fatty Acid-Binding Protein (L-FABP) Gene Expression Is Peroxisome Proliferator-activated Receptor-{alpha}-dependent J. Biol. Chem., October 29, 2004; 279(44): 45512 - 45518. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Hirokane, M. Nakahara, S. Tachibana, M. Shimizu, and R. Sato Bile Acid Reduces the Secretion of Very Low Density Lipoprotein by Repressing Microsomal Triglyceride Transfer Protein Gene Expression Mediated by Hepatocyte Nuclear Factor-4 J. Biol. Chem., October 29, 2004; 279(44): 45685 - 45692. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Sekar and J. D. Veldhuis Involvement of Sp1 and SREBP-1a in transcriptional activation of the LDL receptor gene by insulin and LH in cultured porcine granulosa-luteal cells Am J Physiol Endocrinol Metab, July 1, 2004; 287(1): E128 - E135. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Ledmyr, A. D. McMahon, E. Ehrenborg, L. B. Nielsen, M. Neville, H. Lithell, P. W. MacFarlane, C. J. Packard, F. Karpe, and on behalf of the WOSCOPS executive; The Microsomal Triglyceride Transfer Protein Gene-493T Variant Lowers Cholesterol But Increases the Risk of Coronary Heart Disease Circulation, May 18, 2004; 109(19): 2279 - 2284. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Takeda, K. Obayashi, A. Kobayashi, and M. Maeda A Unique Role of an Amino Terminal 16-Residue Region of Long-Type GATA-6 J. Biochem., May 1, 2004; 135(5): 639 - 650. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yamamoto, H. Shimano, Y. Nakagawa, T. Ide, N. Yahagi, T. Matsuzaka, M. Nakakuki, A. Takahashi, H. Suzuki, H. Sone, et al. SREBP-1 Interacts with Hepatocyte Nuclear Factor-4{alpha} and Interferes with PGC-1 Recruitment to Suppress Hepatic Gluconeogenic Genes J. Biol. Chem., March 26, 2004; 279(13): 12027 - 12035. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Zoltowska, E. Ziv, E. Delvin, M. Lambert, E. Seidman, and E. Levy Both Insulin Resistance and Diabetes in Psammomys obesus Upregulate the Hepatic Machinery Involved in Intracellular VLDL Assembly Arterioscler. Thromb. Vasc. Biol., January 1, 2004; 24(1): 118 - 123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Misawa, T. Horiba, N. Arimura, Y. Hirano, J. Inoue, N. Emoto, H. Shimano, M. Shimizu, and R. Sato Sterol Regulatory Element-binding Protein-2 Interacts with Hepatocyte Nuclear Factor-4 to Enhance Sterol Isomerase Gene Expression in Hepatocytes J. Biol. Chem., September 19, 2003; 278(38): 36176 - 36182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Ameen and J. Oscarsson Sex Difference in Hepatic Microsomal Triglyceride Transfer Protein Expression Is Determined by the Growth Hormone Secretory Pattern in the Rat Endocrinology, September 1, 2003; 144(9): 3914 - 3921. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kang, N. J. Spann, T. Y. Hui, and R. A. Davis ARP-1/COUP-TF II Determines Hepatoma Phenotype by Acting as Both a Transcriptional Repressor of Microsomal Triglyceride Transfer Protein and an Inducer of CYP7A1 J. Biol. Chem., August 15, 2003; 278(33): 30478 - 30486. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Okada, K. Haze, S. Nadanaka, H. Yoshida, N. G. Seidah, Y. Hirano, R. Sato, M. Negishi, and K. Mori A Serine Protease Inhibitor Prevents Endoplasmic Reticulum Stress-induced Cleavage but Not Transport of the Membrane-bound Transcription Factor ATF6 J. Biol. Chem., August 15, 2003; 278(33): 31024 - 31032. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Christoffersen, E. Bollano, M. L. S. Lindegaard, E. D. Bartels, J. P. Goetze, C. B. Andersen, and L. B. Nielsen Cardiac Lipid Accumulation Associated with Diastolic Dysfunction in Obese Mice Endocrinology, August 1, 2003; 144(8): 3483 - 3490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Higashi, H. Itabe, H. Fukase, M. Mori, Y. Fujimoto, and T. Takano Transmembrane Lipid Transfer Is Crucial for Providing Neutral Lipids during Very Low Density Lipoprotein Assembly in Endoplasmic Reticulum J. Biol. Chem., June 6, 2003; 278(24): 21450 - 21458. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hirano, S. Murata, K. Tanaka, M. Shimizu, and R. Sato Sterol Regulatory Element-binding Proteins Are Negatively Regulated through SUMO-1 Modification Independent of the Ubiquitin/26 S Proteasome Pathway J. Biol. Chem., May 2, 2003; 278(19): 16809 - 16819. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.-S. Au, H.-f. Kung, and M. C. Lin Regulation of Microsomal Triglyceride Transfer Protein Gene by Insulin in HepG2 Cells: Roles of MAPKerk and MAPKp38 Diabetes, May 1, 2003; 52(5): 1073 - 1080. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Vecchini, V. Ceccarelli, P. Orvietani, P. Caligiana, F. Susta, L. Binaglia, G. Nocentini, C. Riccardi, and P. Di Nardo Enhanced expression of hepatic lipogenic enzymes in an animal model of sedentariness J. Lipid Res., April 1, 2003; 44(4): 696 - 704. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Wang, F. Liu, C. F. Millette, and D. L. Kilpatrick Expression of a Novel, Sterol-Insensitive Form of Sterol Regulatory Element Binding Protein 2 (SREBP2) in Male Germ Cells Suggests Important Cell- and Stage-Specific Functions for SREBP Targets during Spermatogenesis Mol. Cell. Biol., December 15, 2002; 22(24): 8478 - 8490. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Llorente-Cortes, M. Otero-Vinas, S. Sanchez, C. Rodriguez, and L. Badimon Low-Density Lipoprotein Upregulates Low-Density Lipoprotein Receptor-Related Protein Expression in Vascular Smooth Muscle Cells: Possible Involvement of Sterol Regulatory Element Binding Protein-2-Dependent Mechanism Circulation, December 10, 2002; 106(24): 3104 - 3110. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. N. Ginsberg New Perspectives on Atherogenesis: Role of Abnormal Triglyceride-Rich Lipoprotein Metabolism Circulation, October 15, 2002; 106(16): 2137 - 2142. [Full Text] [PDF]
|
|
|
|
|
|
M. Nakahara, H. Fujii, P. R. Maloney, M. Shimizu, and R. Sato Bile Acids Enhance Low Density Lipoprotein Receptor Gene Expression via a MAPK Cascade-mediated Stabilization of mRNA J. Biol. Chem., September 27, 2002; 277(40): 37229 - 37234. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. L. Lay, I. Lefrere, C. Trautwein, I. Dugail, and S. Krief Insulin and Sterol-regulatory Element-binding Protein-1c (SREBP-1C) Regulation of Gene Expression in 3T3-L1 Adipocytes. IDENTIFICATION OF CCAAT/ENHANCER-BINDING PROTEIN beta AS AN SREBP-1C TARGET J. Biol. Chem., September 13, 2002; 277(38): 35625 - 35634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. B. Nielsen, M. Perko, H. Arendrup, and C. B. Andersen Microsomal Triglyceride Transfer Protein Gene Expression and Triglyceride Accumulation in Hypoxic Human Hearts Arterioscler. Thromb. Vasc. Biol., September 1, 2002; 22(9): 1489 - 1494. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Roglans, E. Sanguino, C. Peris, M. Alegret, M. Vazquez, T. Adzet, C. Diaz, G. Hernandez, J. C. Laguna, and R. M. Sanchez Atorvastatin Treatment Induced Peroxisome Proliferator-Activated Receptor alpha Expression and Decreased Plasma Nonesterified Fatty Acids and Liver Triglyceride in Fructose-Fed Rats J. Pharmacol. Exp. Ther., July 1, 2002; 302(1): 232 - 239. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Lin, E.-J. Wang, C. Lee, K.T. Chin, D. Liu, J.-F. Chiu, and H.-f. Kung Garlic Inhibits Microsomal Triglyceride Transfer Protein Gene Expression in Human Liver and Intestinal Cell Lines and in Rat Intestine J. Nutr., June 1, 2002; 132(6): 1165 - 1168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. F. Lewis, A. Carpentier, K. Adeli, and A. Giacca Disordered Fat Storage and Mobilization in the Pathogenesis of Insulin Resistance and Type 2 Diabetes Endocr. Rev., April 1, 2002; 23(2): 201 - 229. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. D. Bartels, M. Lauritsen, and L. B. Nielsen Hepatic Expression of Microsomal Triglyceride Transfer Protein and In Vivo Secretion of Triglyceride-Rich Lipoproteins Are Increased in Obese Diabetic Mice Diabetes, April 1, 2002; 51(4): 1233 - 1239. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-i. Ito, Y. Nagayasu, K. Kato, R. Sato, and S. Yokoyama Apolipoprotein A-I Induces Translocation of Cholesterol, Phospholipid, and Caveolin-1 to Cytosol in Rat Astrocytes J. Biol. Chem., March 1, 2002; 277(10): 7929 - 7935. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. del Castillo-Olivares and G. Gil Differential Effects of Sterol Regulatory Binding Proteins 1 and 2 on Sterol 12alpha -Hydroxylase. SREBP-2 SUPPRESSES THE STEROL 12alpha -HYDROXYLASE PROMOTER J. Biol. Chem., February 15, 2002; 277(8): 6750 - 6757. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Taghibiglou, F. Rashid-Kolvear, S. C. Van Iderstine, H. Le-Tien, I. G. Fantus, G. F. Lewis, and K. Adeli Hepatic Very Low Density Lipoprotein-ApoB Overproduction Is Associated with Attenuated Hepatic Insulin Signaling and Overexpression of Protein-tyrosine Phosphatase 1B in a Fructose-fed Hamster Model of Insulin Resistance J. Biol. Chem., January 4, 2002; 277(1): 793 - 803. [Abstract] [Full Text]
|
|
|
|
 |
|
 S. Santamarina-Fojo, K. Peterson, C. Knapper, Y. Qiu, L. Freeman, J.-F. Cheng, J. Osorio, A. Remaley, X.-P. Yang, C. Haudenschild, et al. Complete genomic sequence of the human ABCA1 gene: Analysis of the human and mouse ATP-binding cassette A promoter PNAS, July 5, 2000; 97(14): 7987 - 7992. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Sato, A. Okamoto, J. Inoue, W. Miyamoto, Y. Sakai, N. Emoto, H. Shimano, and M. Maeda Transcriptional Regulation of the ATP Citrate-lyase Gene by Sterol Regulatory Element-binding Proteins J. Biol. Chem., April 21, 2000; 275(17): 12497 - 12502. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. B. Raharjo, N. Emoto, K. Ikeda, R. Sato, M. Yokoyama, and M. Matsuo Alternative Splicing Regulates the Endoplasmic Reticulum Localization or Secretion of Soluble Secreted Endopeptidase J. Biol. Chem., June 29, 2001; 276(27): 25612 - 25620. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Hirano, M. Yoshida, M. Shimizu, and R. Sato Direct Demonstration of Rapid Degradation of Nuclear Sterol Regulatory Element-binding Proteins by the Ubiquitin-Proteasome Pathway J. Biol. Chem., September 21, 2001; 276(39): 36431 - 36437. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
