@entity2359 is one of the side-effects of the therapeutically useful antitumour agent, @entity2592 (or @entity9864 , @entity2592 ). This agent is also reported to induce cell @entity204 of cultured neurons. In this study, we show that @entity2592 -induced @entity204 of differentiating @entity35 cerebellar granule neurons is prevented by @entity1880 at concentrations corresponding to its action in preventing protein synthesis. The @entity204 is accompanied by cleavage of the caspase substrate @entity12874 polymerase (PARP) and c-Abl-dependent activation of the stress-activated protein kinases c-Jun N-terminal kinase and @entity12220 . However, c-Jun levels do not rise and the activation of the stress-activated protein kinases is not required for this form of @entity528 . Cyclin-dependent kinase (cdk) activity and inappropriate cell-cycle re-entry have been implicated in some forms of @entity204 in differentiated neurons. Here we show that @entity2592 -induced @entity204 of cerebellar granule neurons is prevented by an inhibitor of @entity19087 , whereas inhibition of @entity69465 mimics the @entity204 , and non- @entity25035 cdks are inhibited by @entity2592 treatment. @entity69466 are dramatically down-regulated during neuronal differentiation, and neither @entity2592 nor inhibition of these cdks induces @entity204 in mature neurons. This mechanism could also play a significant role in the @entity2359 associated with the therapeutic use of @entity2592 , as cdk levels can be upregulated in stressed neurons of adult brain. We propose that the balance between @entity25035 and @entity69465 activity may determine the survival of early differentiating neurons, and that DNA-damaging agents may induce @entity528 by inhibiting @entity69465 under conditions which require these activities for survival.

The mechanism of XXXX -induced apoptosis of differentiating cerebellar granule neurons.

@entity69465 :: ('54237;362817;140908', 'Gene') :: ['cdk1, -2 and -5', 'cdk1/2/5'] @entity12874 :: ('MESH:D011064', 'Chemical') :: ['poly ADP ribose'] @entity1880 :: ('MESH:D003513', 'Chemical') :: ['cycloheximide'] @entity19087 :: ('94201(Tax:10116)', 'Gene') :: ['cdk4'] @entity2592 :: ('MESH:D003561', 'Chemical') :: ['cytarabine', 'Ara-C'] @entity9864 :: ('CHEBI:28680', 'Chemical') :: ['1-beta-d-arabinofuranosyl-cytosine'] @entity25035 :: ('94201;114483', 'Gene') :: ['cdk4/6'] @entity35 :: ('10116', 'Species') :: ['rat'] @entity12220 :: ('81649(Tax:10116)', 'Gene') :: ['p38'] @entity204 :: ('MESH:D003643', 'Disease') :: ['death'] @entity528 :: ('MESH:D009410', 'Disease') :: ['neuronal death'] @entity2359 :: ('MESH:D020258', 'Disease') :: ['neurotoxicity', 'Neurotoxicity'] @entity69466 :: ('54237;362817', 'Gene') :: ['Cdk1 and -2']
@entity2592 :: (MESH:D003561,Chemical) :: ['Ara-C']
