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Identification of a degradation signal at the carboxy terminus of SREBP2: A new role for this domain in cholesterol homeostasis

Kober, Daniel L., Xu, Shimeng, Li, Shili, Bajaj, Bilkish, Liang, Guosheng, Rosenbaum, Daniel M., Radhakrishnan, Arun·2020·Proceedings of the National Academy of Sciences

Abstract

Significance: Sterol regulatory element-binding proteins (SREBPs) are transcription factors that control production of cholesterol and other lipids. In endoplasmic reticulum (ER) membranes, SREBPs form complexes with Scap, a cholesterol-sensing membrane protein. When cholesterol levels are low, Scap escorts SREBPs from the ER to the Golgi where proteolytic cleavage releases the transcription factor domain that turns on genes involved in cholesterol synthesis. The remainder of SREBP still bound to Scap must be eliminated so that Scap can be recycled to bind additional SREBPs. Here, we discover a degradation signal in SREBP that mediates clearance of the cleaved SREBP fragments from Scap. Such clearance is essential for the recycling of Scap and thus it is a central step in regulation of cholesterol homeostasis.

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Crossref · 10.1073/pnas.2018578117

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Research works printed but not linked: 31

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Metadata

Authors
Kober, D. L., Xu, S., Li, S., Bajaj, B., Liang, G., Rosenbaum, D. M., & Radhakrishnan, A.
Affiliations
  • Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390;
  • Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390;
Venue
Proceedings of the National Academy of Sciences
Published
2020-10-26
Volume
117
Issue
45
Pages
28080-28091
ISSN
  • 0027-8424
  • 1091-6490
Cited by
33
References
2
Language
en
Funders
  • HHS | National Institutes of Health (HL20948, GM116387)
  • Welch Foundation (I-1793, I-1770)
  • Fondation Leducq (19CVD04)
  • American Heart Association (18POST34080141)

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