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Regulated proteolysis of p75NTR
Stable Identifier
R-HSA-193692
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
Locations in the PathwayBrowser
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Signal Transduction (Homo sapiens)
Death Receptor Signaling (Homo sapiens)
p75 NTR receptor-mediated signalling (Homo sapiens)
Regulated proteolysis of p75NTR (Homo sapiens)
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p75NTR undergoes a process of regulated intramembrane proteolysis (RIP) similar to other transmembrane proteins such as NOTCH, beta-amyloid precursor protein (APP), and ERBB4. Each of these proteins is subjected to two sequential cleavages. The first one occurs in the extracellular part of the protein and is mediated by the metalloproteinase alpha-secretase which causes shedding of the extracellular domain. The second cleavage occurs in the intramembrane region and is mediated by gamma-secretase and causes release of the intracellular domain, ICD, and of a small peptide. The ICD often traffics to the nucleus and, in some instances (e.g. NOTCH), was found to act as transcriptional regulator. Whether the p75NTR ICD does translocate to the nucleus to regulate gene expression in a way similar to the NOTCH receptor remains to be seen. The alpha- and gamma-secretase mediated cleavage of p75 appears to be regulated by neurotrophin (NGF, BDNF) binding to TRKA or TRKB. p75NTR processing also occurs in response to MAG in cerebellar granule neurons.
Literature References
PubMed ID
Title
Journal
Year
17986144
Metalloproteases and gamma-secretase: new membrane partners regulating p75 neurotrophin receptor signaling?
Bronfman, FC
J Neurochem
2007
Participants
Events
alpha-secretase cleaves the p75NTR extracellular domain
(Homo sapiens)
The p75NTR C-terminal fragment enters endosomes
(Homo sapiens)
gamma-secretase cleaves the p75NTR transmembrane domain
(Homo sapiens)
p75NTR ICD signals to NF-kB
(Homo sapiens)
Part of the ICD migrates to the nucleus
(Homo sapiens)
Participates
as an event of
p75 NTR receptor-mediated signalling (Homo sapiens)
Event Information
Go Biological Process
membrane protein intracellular domain proteolysis (0031293)
Orthologous Events
Regulated proteolysis of p75NTR (Bos taurus)
Regulated proteolysis of p75NTR (Canis familiaris)
Regulated proteolysis of p75NTR (Danio rerio)
Regulated proteolysis of p75NTR (Gallus gallus)
Regulated proteolysis of p75NTR (Mus musculus)
Regulated proteolysis of p75NTR (Rattus norvegicus)
Regulated proteolysis of p75NTR (Sus scrofa)
Regulated proteolysis of p75NTR (Xenopus tropicalis)
Authored
Nasi, S (2006-10-10)
Annibali, D (2006-10-10)
Reviewed
Friedman, WJ (2008-05-20)
Chao, MV (2008-05-28)
Created
Jassal, B (2007-02-23)
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