Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.62 (caspase-9)
 7,507 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclin-dependent kinase 5 (Cdk5) is a member of the cyclin-dependent kinase family that is mostly seen in neurons, does not vary with cell cycle, and is activated in many neurodegenerative disorders and other non-neuronal pathologies, but its relationship to non-neuronal apoptosis is not understood, nor is the control of the activation of Cdk5 by its activators. The most widely studied activator of Cdk5, p35, is cleaved to p25 by calpain, an event that has been linked with activation of Cdk5 and neuronal death. Here we report that calpain-mediated Cdk5/p25 activation accompanies non-neuronal as well as neuronal cell death, suggesting that the p35/calpain/p25/Cdk5 activation sequence is a general feature of cell death. We further demonstrate that Cdk5 can be activated in the absence of p53, Apaf-1, caspase-9, and -3 during cell death, indicating that its activation relates more to cell death than to a specific pathway of apoptosis.
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PMID:p53, Apaf-1, caspase-3, and -9 are dispensable for Cdk5 activation during cell death. 1602 Nov 78

Cyclin-dependent kinase 5 regulatory subunit associated protein 1 (CDK5RAP1) is an enzyme which post-synthetically converts the RNA modification N6-iso-pentenyladenosine (i6A) into 2-methylthio-N6-isopentenyladenosine (ms2i6A). However, the interaction between CDK5RAP1 deficiency and cell apoptosis has not been studied. Breast cancer has long been a leading cause of mortality in the world. Therefore, in the present study, CDK5RAP1 deficiency in a human breast cancer cell line was investigated. CDK5RAP1 small interfering RNA (siRNA) and negative control siRNA were transfected into MCF-7 cells, and the cells were further incubated for 48 h. CDK5RAP1 deficiency suppressed tumor growth in MCF-7 cells and arrested the cells at G2/M phase. CDK5RAP1 deficiency also induced cell apoptosis and reactive oxygen species (ROS) generation. Furthermore, western blot analysis showed that the expression of phospho-c-Jun N-terminal kinase (p-JNK), p53, caspase-9 and caspase-3 were upregulated in CDK5RAP1-deficient MCF-7 cells. Pretreatment with N-acetyl-cysteine (NAC), the inhibitor of ROS, or with SP600125, the inhibitor of JNK, prevented the apoptosis and the high expression of p-JNK, p53, caspase-9 and caspase-3 in CDK5RAP1-deficient MCF-7 cells. Taken together, these data indicated that CDK5RAP1 deficiency induced cell cycle arrest and apoptosis in human breast cancer MCF-7 cells by the ROS/JNK signaling pathway. Our findings indicated a novel therapeutic strategy for cancer.
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PMID:CDK5RAP1 deficiency induces cell cycle arrest and apoptosis in human breast cancer cell line by the ROS/JNK signaling pathway. 2560 31