Regulation of Fibroblast Activation Protein-α Expression: Focus on Intracellular Protein Interactions.

Details

Serval ID
serval:BIB_5E461AB849B4
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Regulation of Fibroblast Activation Protein-α Expression: Focus on Intracellular Protein Interactions.
Journal
Journal of medicinal chemistry
Author(s)
Juillerat-Jeanneret L., Tafelmeyer P., Golshayan D.
ISSN
1520-4804 (Electronic)
ISSN-L
0022-2623
Publication state
Published
Issued date
14/10/2021
Peer-reviewed
Oui
Volume
64
Number
19
Pages
14028-14045
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't ; Review
Publication Status: ppublish
Abstract
The prolyl-specific peptidase fibroblast activation protein-α (FAP-α) is expressed at very low or undetectable levels in nondiseased human tissues but is selectively induced in activated (myo)fibroblasts at sites of tissue remodeling in fibrogenic processes. In normal regenerative processes involving transient fibrosis FAP-α <sup>+</sup> (myo)fibroblasts disappear from injured tissues, replaced by cells with a normal FAP-α <sup>-</sup> phenotype. In chronic uncontrolled pathological fibrosis FAP-α <sup>+</sup> (myo)fibroblasts permanently replace normal tissues. The mechanisms of regulation and elimination of FAP-α expression in(myo)fibroblasts are unknown. According to a yeast two-hybrid screen and protein databanks search, we propose that the intracellular (co)-chaperone BAG6/BAT3 can interact with FAP-α, mediated by the BAG6/BAT3 Pro-rich domain, inducing proteosomal degradation of FAP-α protein under tissue homeostasis. In this Perspective, we discuss our findings in the context of current knowledge on the regulation of FAP-α expression and comment potential therapeutic strategies for uncontrolled fibrosis, including small molecule degraders (PROTACs)-modified FAP-α targeted inhibitors.
Keywords
Endopeptidases/genetics, Endopeptidases/metabolism, Humans, Membrane Proteins/genetics, Membrane Proteins/metabolism, Models, Molecular, Molecular Chaperones/metabolism, Protein Binding
Pubmed
Web of science
Create date
16/09/2021 15:54
Last modification date
21/12/2021 6:34
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