Calpain cleaves p35 to p25

Stable Identifier
R-HSA-8863012
Type
Reaction [transition]
Species
Homo sapiens
Compartment
cytosol
ReviewStatus
5/5
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Calpain cleaves p35 to p25
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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

Peng, J, Kwon, YT, Friedlander, RM, Lee, MS, Li, M, Tsai, LH

Nature 2000
Participants
Input
Output
Participates
as an event of
Catalyst Activity

calcium-dependent cysteine-type endopeptidase activity of Calpain1, Calpain2:Ca2+ [plasma membrane]

Physical Entity
Calpain1, Calpain2:Ca2+ [plasma membrane] (Homo sapiens)
Activity
calcium-dependent cysteine-type endopeptidase activity (GO:0004198)
This event is regulated
Negatively by
Regulator
Calpain1,Calpain2:Ca2+:CAST [plasma membrane] (Homo sapiens)
Inferred From
Calpain 1 or Calpain 2 cleaves Cdk5r1 (p35) (Mus musculus)
Disease
Name Identifier Synonyms
Alzheimer's disease DOID:10652 AD, Alzheimers dementia, Alzheimer disease
Authored
Shah, K  (2016-02-23)
Created
Orlic-Milacic, M  (2016-03-03)
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