Id |
Subject |
Object |
Predicate |
Lexical cue |
T1 |
0-80 |
Sentence |
denotes |
Calpain-mediated cleavage of the cyclin-dependent kinase-5 activator p39 to p29. |
T2 |
81-201 |
Sentence |
denotes |
The activity of cyclin-dependent kinase-5 (Cdk5) is tightly regulated by binding of its neuronal activators p35 and p39. |
T3 |
202-471 |
Sentence |
denotes |
Upon neurotoxic insults, p35 is cleaved to p25 by the Ca(2+)-dependent protease calpain. p25 is accumulated in ischemic brains and in brains of patients with Alzheimer's disease. p25 deregulates Cdk5 activity by causing prolonged activation and mislocalization of Cdk5. |
T4 |
472-626 |
Sentence |
denotes |
It is unknown whether p39, which is expressed throughout the adult rat brain, is cleaved by calpain, and whether this contributes to deregulation of Cdk5. |
T5 |
627-729 |
Sentence |
denotes |
Here, we show that calpain cleaved p39 in vitro, resulting in generation of a C-terminal p29 fragment. |
T6 |
730-819 |
Sentence |
denotes |
In vivo, p29 was generated in ischemic brain concomitant with increased calpain activity. |
T7 |
820-932 |
Sentence |
denotes |
In fresh brain lysates, generation of p29 was Ca(2+)-dependent, and calpain inhibitors abolished p29 production. |
T8 |
933-1082 |
Sentence |
denotes |
The Ca(2+) ionophore ionomycin and the excitotoxin glutamate induced production of p29 in cultures of cortical neurons in a calpain-dependent manner. |
T9 |
1083-1176 |
Sentence |
denotes |
Like p25, p29 was more stable than p39 and caused redistribution of Cdk5 in cortical neurons. |
T10 |
1177-1316 |
Sentence |
denotes |
Our data suggest that neurotoxic insults lead to calpain-mediated conversion of p39 to p29, which might contribute to deregulation of Cdk5. |