The SREBP pathway. gene regulation through sterol sensing and gated protein trafficking

Arun Radhakrishnan, Li Ping Sun, Peter Espenshade, Joseph L. Goldstein, Michael S. Brown

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Cholesterol is an essential component of mammalian cell membranes. Sufficient levels of cellular cholesterol are required for the integrity and impermeability of the plasma membrane, for the proper assembly of cell surface lipid rafts and caveolae, and for the posttranslational modification of at least one protein, the morphogen Hedgehog. Regulation of cholesterol levels in the body is highly essential. In this regard, this chapter outlines the molecular mechanism that mammalian cells utilize to maintain proper cholesterol homeostasis. Sterol regulatory element-binding proteins (SREBPs) transmit information to the nucleus about the sterol content of membranes. To date, in mammalian cells SREBPs have been shown to directly activate more than thirty genes involved in the synthesis and uptake of cholesterol, fatty acids, triglycerides, and phospholipids. The SREBP pathway has also been identified and studied in cells of non-vertebrates including yeast, worms, and insects. This chapter focuses on mammals. It describes the mechanism for sterol mediated regulation of the processing of SREBP. Finally, the study states that the molecular switch that controls sterol metabolism in animal cells is a simple hexapeptide targeting signal (MELADL) in a single membrane protein (Scap). Future research areas need to be targeted at exploring the question of how the Scap and Insig discriminate between cholesterol and oxysterol and what is the nature of the conformational change upon sterol binding that allows complex formation. The answers to these questions await detailed molecular structures of Scap, Insig, and the Scap-Insig complex.

Original languageEnglish (US)
Title of host publicationHandbook of Cell Signaling, 2/e
PublisherElsevier Inc.
Pages2505-2510
Number of pages6
Volume3
ISBN (Print)9780123741455
DOIs
StatePublished - 2010

Fingerprint

Sterol Regulatory Element Binding Proteins
Sterols
Protein Transport
Gene expression
Cholesterol
Genes
Proteins
Cells
Cell membranes
Hedgehog Proteins
Cell Membrane
Caveolae
Mammals
Post Translational Protein Processing
Molecular Structure
Metabolism
Yeast
Molecular structure
Insects
Phospholipids

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Radhakrishnan, A., Sun, L. P., Espenshade, P., Goldstein, J. L., & Brown, M. S. (2010). The SREBP pathway. gene regulation through sterol sensing and gated protein trafficking. In Handbook of Cell Signaling, 2/e (Vol. 3, pp. 2505-2510). Elsevier Inc.. https://doi.org/10.1016/B978-0-12-374145-5.00298-9

The SREBP pathway. gene regulation through sterol sensing and gated protein trafficking. / Radhakrishnan, Arun; Sun, Li Ping; Espenshade, Peter; Goldstein, Joseph L.; Brown, Michael S.

Handbook of Cell Signaling, 2/e. Vol. 3 Elsevier Inc., 2010. p. 2505-2510.

Research output: Chapter in Book/Report/Conference proceedingChapter

Radhakrishnan, A, Sun, LP, Espenshade, P, Goldstein, JL & Brown, MS 2010, The SREBP pathway. gene regulation through sterol sensing and gated protein trafficking. in Handbook of Cell Signaling, 2/e. vol. 3, Elsevier Inc., pp. 2505-2510. https://doi.org/10.1016/B978-0-12-374145-5.00298-9
Radhakrishnan A, Sun LP, Espenshade P, Goldstein JL, Brown MS. The SREBP pathway. gene regulation through sterol sensing and gated protein trafficking. In Handbook of Cell Signaling, 2/e. Vol. 3. Elsevier Inc. 2010. p. 2505-2510 https://doi.org/10.1016/B978-0-12-374145-5.00298-9
Radhakrishnan, Arun ; Sun, Li Ping ; Espenshade, Peter ; Goldstein, Joseph L. ; Brown, Michael S. / The SREBP pathway. gene regulation through sterol sensing and gated protein trafficking. Handbook of Cell Signaling, 2/e. Vol. 3 Elsevier Inc., 2010. pp. 2505-2510
@inbook{c28d0874a25c4068bb084fb3e003d8f4,
title = "The SREBP pathway. gene regulation through sterol sensing and gated protein trafficking",
abstract = "Cholesterol is an essential component of mammalian cell membranes. Sufficient levels of cellular cholesterol are required for the integrity and impermeability of the plasma membrane, for the proper assembly of cell surface lipid rafts and caveolae, and for the posttranslational modification of at least one protein, the morphogen Hedgehog. Regulation of cholesterol levels in the body is highly essential. In this regard, this chapter outlines the molecular mechanism that mammalian cells utilize to maintain proper cholesterol homeostasis. Sterol regulatory element-binding proteins (SREBPs) transmit information to the nucleus about the sterol content of membranes. To date, in mammalian cells SREBPs have been shown to directly activate more than thirty genes involved in the synthesis and uptake of cholesterol, fatty acids, triglycerides, and phospholipids. The SREBP pathway has also been identified and studied in cells of non-vertebrates including yeast, worms, and insects. This chapter focuses on mammals. It describes the mechanism for sterol mediated regulation of the processing of SREBP. Finally, the study states that the molecular switch that controls sterol metabolism in animal cells is a simple hexapeptide targeting signal (MELADL) in a single membrane protein (Scap). Future research areas need to be targeted at exploring the question of how the Scap and Insig discriminate between cholesterol and oxysterol and what is the nature of the conformational change upon sterol binding that allows complex formation. The answers to these questions await detailed molecular structures of Scap, Insig, and the Scap-Insig complex.",
author = "Arun Radhakrishnan and Sun, {Li Ping} and Peter Espenshade and Goldstein, {Joseph L.} and Brown, {Michael S.}",
year = "2010",
doi = "10.1016/B978-0-12-374145-5.00298-9",
language = "English (US)",
isbn = "9780123741455",
volume = "3",
pages = "2505--2510",
booktitle = "Handbook of Cell Signaling, 2/e",
publisher = "Elsevier Inc.",

}

TY - CHAP

T1 - The SREBP pathway. gene regulation through sterol sensing and gated protein trafficking

AU - Radhakrishnan, Arun

AU - Sun, Li Ping

AU - Espenshade, Peter

AU - Goldstein, Joseph L.

AU - Brown, Michael S.

PY - 2010

Y1 - 2010

N2 - Cholesterol is an essential component of mammalian cell membranes. Sufficient levels of cellular cholesterol are required for the integrity and impermeability of the plasma membrane, for the proper assembly of cell surface lipid rafts and caveolae, and for the posttranslational modification of at least one protein, the morphogen Hedgehog. Regulation of cholesterol levels in the body is highly essential. In this regard, this chapter outlines the molecular mechanism that mammalian cells utilize to maintain proper cholesterol homeostasis. Sterol regulatory element-binding proteins (SREBPs) transmit information to the nucleus about the sterol content of membranes. To date, in mammalian cells SREBPs have been shown to directly activate more than thirty genes involved in the synthesis and uptake of cholesterol, fatty acids, triglycerides, and phospholipids. The SREBP pathway has also been identified and studied in cells of non-vertebrates including yeast, worms, and insects. This chapter focuses on mammals. It describes the mechanism for sterol mediated regulation of the processing of SREBP. Finally, the study states that the molecular switch that controls sterol metabolism in animal cells is a simple hexapeptide targeting signal (MELADL) in a single membrane protein (Scap). Future research areas need to be targeted at exploring the question of how the Scap and Insig discriminate between cholesterol and oxysterol and what is the nature of the conformational change upon sterol binding that allows complex formation. The answers to these questions await detailed molecular structures of Scap, Insig, and the Scap-Insig complex.

AB - Cholesterol is an essential component of mammalian cell membranes. Sufficient levels of cellular cholesterol are required for the integrity and impermeability of the plasma membrane, for the proper assembly of cell surface lipid rafts and caveolae, and for the posttranslational modification of at least one protein, the morphogen Hedgehog. Regulation of cholesterol levels in the body is highly essential. In this regard, this chapter outlines the molecular mechanism that mammalian cells utilize to maintain proper cholesterol homeostasis. Sterol regulatory element-binding proteins (SREBPs) transmit information to the nucleus about the sterol content of membranes. To date, in mammalian cells SREBPs have been shown to directly activate more than thirty genes involved in the synthesis and uptake of cholesterol, fatty acids, triglycerides, and phospholipids. The SREBP pathway has also been identified and studied in cells of non-vertebrates including yeast, worms, and insects. This chapter focuses on mammals. It describes the mechanism for sterol mediated regulation of the processing of SREBP. Finally, the study states that the molecular switch that controls sterol metabolism in animal cells is a simple hexapeptide targeting signal (MELADL) in a single membrane protein (Scap). Future research areas need to be targeted at exploring the question of how the Scap and Insig discriminate between cholesterol and oxysterol and what is the nature of the conformational change upon sterol binding that allows complex formation. The answers to these questions await detailed molecular structures of Scap, Insig, and the Scap-Insig complex.

UR - http://www.scopus.com/inward/record.url?scp=84882906886&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84882906886&partnerID=8YFLogxK

U2 - 10.1016/B978-0-12-374145-5.00298-9

DO - 10.1016/B978-0-12-374145-5.00298-9

M3 - Chapter

SN - 9780123741455

VL - 3

SP - 2505

EP - 2510

BT - Handbook of Cell Signaling, 2/e

PB - Elsevier Inc.

ER -