IRE1β Inhibits Chylomicron Production by Selectively Degrading MTP mRNA

Iqbal, Jahangir; Dai, Kezhi; Seimon, Tracie A.; Jungreis, Rivka; Oyadomari, Miho; Kuriakose, George; Ron, David; Tabas, Ira; Hussain, M. Mahmood

doi:10.1016/j.cmet.2008.03.005

Cited by 127 publications

(126 citation statements)

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“…Although it has been reported that IRE1a and IRE1b are involved in the degradation of ER-localized mRNA [11][12][13][14][15][16], is there any difference in substrate between IRE1a and IRE1b? In our study, hIRE1b decreased the ER-localized Fluc-ER mRNA while hIRE1a had little effect on Fluc-ER mRNA (Fig.…”

Section: Discussionmentioning

confidence: 99%

Mammalian ER stress sensor IRE1β specifically down-regulates the synthesis of secretory pathway proteins

et al. 2010

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Edited by Robert Barouki Keywords:Endoplasmic reticulum stress Unfolded protein response IRE1b Secretory proteins a b s t r a c t Accumulation of unfolded proteins in the endoplasmic reticulum (ER) causes ER stress. The ER stress sensor inositol requiring enzyme-1beta (IRE1b), which is specifically expressed in intestinal epithelial cells, is thought to be involved in translational repression. However, its mechanism of action is not fully understood. Using a reporter that can evaluate and distinguish between translation efficiency in the cytosol and on the ER membrane, we show here that IRE1b represses translation on the ER membrane but not in the cytosol, and that this selective repression depends on the RNase activity of IRE1b.

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Section: Discussionmentioning

confidence: 99%

Mammalian ER stress sensor IRE1β specifically down-regulates the synthesis of secretory pathway proteins

et al. 2010

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“…It should be pointed out MTP mRNA levels have been shown to be regulated involving transcriptional (44,45) as well as post-transcriptional mechanisms (6,46). Hence, it is possible that LysoPC might increase hepatic MTP gene transcription.…”

Section: Discussionmentioning

confidence: 99%

Lysophosphatidylcholine Acyltransferase 3 Knockdown-mediated Liver Lysophosphatidylcholine Accumulation Promotes Very Low Density Lipoprotein Production by Enhancing Microsomal Triglyceride Transfer Protein Expression

Ding

Pan

et al. 2012

Journal of Biological Chemistry

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“…They also found evidence suggesting that PL recruitment is intrinsic in the NH 2 -terminal domain of apoB during the translational process and may facilitate protein folding. Recently, we showed that a deficiency in inositol-requiring enzyme 1␤ (IRE1␤) in mice placed on a high-fat, high-cholesterol diet enhances intestinal MTP expression, which leads to increased lipid absorption and chylomicron secretion (92). IRE1␤ was shown to cause endolytic cleavage of MTP mRNA between exons 2 and 7.…”

Section: Assembly Secretion and Regulation Of Intestinal Lipoproteinsmentioning

confidence: 99%

Intestinal lipid absorption

Iqbal¹,

Hussain²

2009

American Journal of Physiology-Endocrinology and Metabolism

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Our knowledge of the uptake and transport of dietary fat and fat-soluble vitamins has advanced considerably. Researchers have identified several new mechanisms by which lipids are taken up by enterocytes and packaged as chylomicrons for export into the lymphatic system or clarified the actions of mechanisms previously known to participate in these processes. Fatty acids are taken up by enterocytes involving protein-mediated as well as proteinindependent processes. Net cholesterol uptake depends on the competing activities of NPC1L1, ABCG5, and ABCG8 present in the apical membrane. We have considerably more detailed information about the uptake of products of lipid hydrolysis, the active transport systems by which they reach the endoplasmic reticulum, the mechanisms by which they are resynthesized into neutral lipids and utilized within the endoplasmic reticulum to form lipoproteins, and the mechanisms by which lipoproteins are secreted from the basolateral side of the enterocyte. apoB and MTP are known to be central to the efficient assembly and secretion of lipoproteins. In recent studies, investigators found that cholesterol, phospholipids, and vitamin E can also be secreted from enterocytes as components of high-density apoB-free/apoAI-containing lipoproteins. Several of these advances will probably be investigated further for their potential as targets for the development of drugs that can suppress cholesterol absorption, thereby reducing the risk of hypercholesterolemia and cardiovascular disease.intestine; dietary fat; triacylglycerol; cholesterol; phospholipids; fat-soluble vitamins; microsomal triglyceride transfer protein DIETARY FATS CONSIST OF A WIDE ARRAY of polar and nonpolar lipids (32, 33). Triacylglycerol (TAG) is the dominant fat in the diet, contributing 90 -95% of the total energy derived from dietary fat. Dietary fats also include phospholipids (PLs), sterols (e.g., cholesterol), and many other lipids (e.g., fatsoluble vitamins). The predominant PL in the intestinal lumen is phosphatidylcholine (PC), which is derived mostly from bile (10 -20 g/day in humans) but also from the diet (ϳ1-2 g/day). The predominant dietary sterols are cholesterol (mostly of animal origin) and ␤-sitosterol (the major plant sterol). Although ␤-sitosterol accounts for 25% of dietary sterols, it is not absorbed by humans under physiological conditions.Researchers have been investigating the various steps involved in lipid digestion, absorption, and metabolism to identify factors that could serve as targets for the development of drugs capable of reducing the risk of lipid-associated disorders, including dyslipidemias and cardiovascular disease. In so doing, they have explored key aspects of lipid digestion hydrolysis, emulsification, and micelle formation. They have also explored key issues of absorption, e.g., the uptake of the products of lipid hydrolysis by enterocytes (the epithelial cells lining the walls of the intestinal lumen) and their transport to intracellular compartments, where fatty acids and sterols are...

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IRE1β Inhibits Chylomicron Production by Selectively Degrading MTP mRNA

Cited by 127 publications

References 49 publications

Mammalian ER stress sensor IRE1β specifically down-regulates the synthesis of secretory pathway proteins

Mammalian ER stress sensor IRE1β specifically down-regulates the synthesis of secretory pathway proteins

Lysophosphatidylcholine Acyltransferase 3 Knockdown-mediated Liver Lysophosphatidylcholine Accumulation Promotes Very Low Density Lipoprotein Production by Enhancing Microsomal Triglyceride Transfer Protein Expression

Intestinal lipid absorption

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