scholarly journals Upregulation of Bone Morphogenetic Protein-1/Mammalian Tolloid and Procollagen C-Proteinase Enhancer-1 in Corneal Scarring

2014 ◽  
Vol 55 (10) ◽  
pp. 6712-6721 ◽  
Author(s):  
F. Malecaze ◽  
D. Massoudi ◽  
P. Fournie ◽  
C. Tricoire ◽  
M. Cassagne ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Corneal Scarring ◽  
Morphogenetic Protein ◽  
Bone Morphogenetic Protein 1

The Drosophila dorsal-ventral patterning gene tolloid is related to human bone morphogenetic protein 1

Cell ◽  
1991 ◽  
Vol 67 (3) ◽  
pp. 469-481 ◽  
Author(s):  
Mary Jane Shimell ◽  
Edwin L. Ferguson ◽  
Steven R. Childs ◽  
Michael B. O'Connor
Keyword(s):  
Bone Morphogenetic Protein ◽  
Human Bone ◽  
Morphogenetic Protein ◽  
Human Bone Morphogenetic Protein ◽  
Bone Morphogenetic Protein 1

Bone morphogenetic protein 1 cleaves the linker region between ligand-binding repeats 4 and 5 of the LDL receptor and makes the LDL receptor non-functional

2019 ◽  
Vol 29 (8) ◽  
pp. 1229-1238
Author(s):  
Thea Bismo Strøm ◽  
Katrine Bjune ◽  
Trond P Leren
Keyword(s):  
Ligand Binding ◽  
Bone Morphogenetic Protein ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Low Density ◽  
Linker Region ◽  
Cholesterol Levels ◽  
Morphogenetic Protein ◽  
Bone Morphogenetic Protein 1

Abstract The cell-surface low-density lipoprotein receptor (LDLR) internalizes low-density lipoprotein (LDL) by receptor-mediated endocytosis and plays a key role in the regulation of plasma cholesterol levels. The ligand-binding domain of the LDLR contains seven ligand-binding repeats of approximately 40 residues each. Between ligand-binding repeats 4 and 5, there is a 10-residue linker region that is subject to enzymatic cleavage. The cleaved LDLR is unable to bind LDL. In this study, we have screened a series of enzyme inhibitors in order to identify the enzyme that cleaves the linker region. These studies have identified bone morphogenetic protein 1 (BMP1) as being the cleavage enzyme. This conclusion is based upon the use of the specific BMP1 inhibitor UK 383367, silencing of the BMP1 gene by the use of siRNA or CRISPR/Cas9 technology and overexpression of wild-type BMP1 or the loss-of-function mutant E214A-BMP1. We have also shown that the propeptide of BMP1 has to be cleaved at RSRR120↓ by furin-like proprotein convertases for BMP1 to have an activity towards the LDLR. Targeting BMP1 could represent a novel strategy to increase the number of functioning LDLRs in order to lower plasma LDL cholesterol levels. However, a concern by using BMP1 inhibitors as cholesterol-lowering drugs could be the risk of side effects based on the important role of BMP1 in collagen assembly.

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