PMID- 11909854
OWN - NLM
STAT- MEDLINE
DCOM- 20020712
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 277
IP  - 23
DP  - 2002 Jun 7
TI  - A novel, extraneuronal role for cyclin-dependent protein kinase 5 (CDK5): 
      modulation of cAMP-induced apoptosis in rat leukemia cells.
PG  - 20783-93
AB  - A number of cyclin-dependent protein kinase (CDK) inhibitors were tested for the 
      ability to protect IPC-81 rat leukemic cells against cAMP-induced apoptosis. A 
      near perfect proportionality was observed between inhibitor potency to protect 
      against cAMP-induced apoptosis and to antagonize CDK5, and to a lesser extent, 
      CDK2 and CDK1. Enforced expression of dominant negative CDK5 (but not CDK1-dn or 
      CDK2-dn) protected against death, indicating that CDK5 activity was necessary for 
      cAMP-induced apoptosis. The CDK inhibitors failed to protect the cells against 
      daunorubicine-, staurosporine-, or okadaic acid-induced apoptosis. The inhibition 
      of CDK5 prevented the cleavage of pro-caspase-3 in cAMP-treated cells. The cells 
      could be saved closer to the moment of their onset of death by inhibitors of 
      caspases than by inhibitors of CDK5. This suggested that the action of CDK5 was 
      upstream of caspase activation. The cAMP treatment resulted in a moderate 
      increase of the level of CDK5 mRNA and protein in IPC-81 wild-type cells. Such 
      cAMP induction of CDK5 was not observed in cells expressing the inducible cAMP 
      early repressor. The cAMP-induced increase of CDK5 contributed to apoptosis since 
      cells overexpressing CDK5-wt were more sensitive for cAMP-induced death. These 
      results demonstrate the first example of a proapoptotic CDK action upstream of 
      caspase activation and of an extra-neuronal effect of CDK5.
FAU - Sandal, Tone
AU  - Sandal T
AD  - Department of Anatomy and Cell Biology, University of Bergen, Bergen, 5009 
      Norway.
FAU - Stapnes, Camilla
AU  - Stapnes C
FAU - Kleivdal, Hans
AU  - Kleivdal H
FAU - Hedin, Lars
AU  - Hedin L
FAU - Doskeland, Stein Ove
AU  - Doskeland SO
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20020321
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Thionucleotides)
RN  - 41941-66-6 (8-((4-chlorophenyl)thio)cyclic-3',5'-AMP)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.1 (Cyclin-Dependent Kinase 5)
RN  - EC 2.7.11.22 (Cdk5 protein, rat)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects/*physiology
MH  - Caspases/metabolism
MH  - Cyclic AMP/*analogs & derivatives/pharmacology
MH  - Cyclin-Dependent Kinase 5
MH  - Cyclin-Dependent Kinases/antagonists & inhibitors/*physiology
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/pharmacology
MH  - Leukemia, Promyelocytic, Acute/*pathology
MH  - Neurons/enzymology
MH  - Rats
MH  - Thionucleotides/pharmacology
MH  - Tumor Cells, Cultured
EDAT- 2002/03/23 10:00
MHDA- 2002/07/13 10:01
CRDT- 2002/03/23 10:00
PHST- 2002/03/23 10:00 [pubmed]
PHST- 2002/07/13 10:01 [medline]
PHST- 2002/03/23 10:00 [entrez]
AID - S0021-9258(20)84930-8 [pii]
AID - 10.1074/jbc.M112248200 [doi]
PST - ppublish
SO  - J Biol Chem. 2002 Jun 7;277(23):20783-93. doi: 10.1074/jbc.M112248200. Epub 2002 
      Mar 21.