Calpain cleaves p35 to p25

Stable Identifier
R-HSA-8863012
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

A variety of neurotoxic insults such as beta-amyloid (A-beta), ischemia, excitotoxicity and oxidative stress disrupt the intracellular calcium homeostasis in neurons, thereby leading to the activation of calpain, which cleaves p35 into p25 and p10 (Lee et al. 2000). p25 has a six-fold longer half-life compared to p35 and lacks the membrane anchoring signal, which results in its constitutive activation and mislocalization of the CDK5:p25 complex to the cytoplasm and the nucleus.

Calpain-mediated cleavage of p35 to p25 is inhibited by calpastatin (CAST). CAST levels are decreased in Alzheimer disease (Sato et al. 2011).

Literature References
PubMed ID Title Journal Year
10830966 Neurotoxicity induces cleavage of p35 to p25 by calpain Nature 2000
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
calcium-dependent cysteine-type endopeptidase activity of Calpain1, Calpain2:Ca2+ [plasma membrane]
Physical Entity
Activity
This entity is regulated by
Inferred From
Disease
Name Identifier Synonyms
Alzheimer's disease 10652 AD, Alzheimers dementia, Alzheimer disease