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The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Strategies to prevent cleavage of the linker region between ligand-binding repeats 4 and 5 of the LDL receptor

Strøm, Thea Bismo, Bjune, Katrine, Costa, Luís Teixeira da, Leren, Trond P·2019·Human Molecular Genetics
DOI 10.1093/hmg/ddz164
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Abstract

A main strategy for lowering plasma low-density lipoprotein (LDL) cholesterol levels is to increase the number of cell-surface LDL receptors (LDLRs). This can be achieved by increasing the synthesis or preventing the degradation of the LDLR. One mechanism by which an LDLR becomes non-functional is enzymatic cleavage within the 10 residue linker region between ligand-binding repeats 4 and 5. The cleaved LDLR has only three ligand-binding repeats and is unable to bind LDL. In this study, we have performed cell culture experiments to identify strategies to prevent this cleavage. As a part of these studies, we found that Asp193 within the linker region is critical for cleavage to occur. Moreover, both 14-mer synthetic peptides and antibodies directed against the linker region prevented cleavage. As a consequence, more functional LDLRs were observed on the cell surface. The observation that the cleaved LDLR was present in extracts from the human adrenal gland indicates that cleavage of the linker region takes place in vivo. Thus, preventing cleavage of the LDLR by pharmacological measures could represent a novel lipid-lowering strategy.

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Crossref · 10.1093/hmg/ddz164

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  • Blocking the action of BMP1 on LDLR could represent a novel approach to reducing plasma LDL-cholesterol.

    “Both 14-mer synthetic peptides and antibodies directed against the linker region between LA repeats 4 and 5 prevented cleavage of LDLR by BMP1, providing proof of principle that blocking the action of BMP1 on LDLR could represent a novel approach to reducing plasma LDL-cholesterol [64].”

    From Post-translational regulation of the low-density lipoprotein receptor provides new targets for cholesterol regulation (2024) · cites this paper as [64]

  • Both 14-mer synthetic peptides and antibodies directed against the linker region between LA repeats 4 and 5 prevented cleavage of LDLR by BMP1.

    “Both 14-mer synthetic peptides and antibodies directed against the linker region between LA repeats 4 and 5 prevented cleavage of LDLR by BMP1, providing proof of principle that blocking the action of BMP1 on LDLR could represent a novel approach to reducing plasma LDL-cholesterol [64].”

    From Post-translational regulation of the low-density lipoprotein receptor provides new targets for cholesterol regulation (2024) · cites this paper as [64]

  • The LDLR is cleaved in the linker region between LA repeat 4 and 5, with Asp193 being crucial for this cleavage.

    “Multiple studies have shown that the LDLR is cleaved in the linker region between LA repeat 4 and 5 [107], with Asp193 being crucial for this cleavage [56,106].”

    From The low-density lipoprotein receptor: Emerging post-transcriptional regulatory mechanisms (2025) · cites this paper as [106]

  • Synthetic peptides and antibodies against the linker region containing the BMP1 cleavage site prevented cleavage of LDLR by BMP1.

    “Indeed, synthetic peptides and antibodies against the linker region containing the BMP1 cleavage site, prevented cleavage of LDLR by BMP1, providing important evidence that blocking BMP1 action on LDLR could be a possible novel avenue to target reducing plasma LDL-C levels112.”

    From Pathways and Molecular Mechanisms Governing LDL Receptor Regulation (2025) · cites this paper as [112]

  • Blocking BMP1 action on LDLR could be a possible novel avenue to target reducing plasma LDL-C levels.

    “providing important evidence that blocking BMP1 action on LDLR could be a possible novel avenue to target reducing plasma LDL-C levels112.”

    From Pathways and Molecular Mechanisms Governing LDL Receptor Regulation (2025) · cites this paper as [112]

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Metadata

Authors
Strøm, T. B., Bjune, K., Costa, L. T. D., & Leren, T. P.
Affiliations
Unit for Cardiac and Cardiovascular Genetics, Department of Medical Genetics, Oslo University Hospital, Oslo, Norway
Venue
Human Molecular Genetics
Publisher
Oxford University Press (OUP)
Published
2019-07-23
Volume
28
Issue
22
Pages
3734-3741
ISSN
  • 0964-6906
  • 1460-2083
DOI
10.1093/hmg/ddz164
Cited by
6
References
1
Language
en
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)

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