TY  - JOUR
A1  - Hamdane, Malika
A1  - Bretteville, Alexis
A1  - Sambo, Anne-Véronique
A1  - Schindowski, Katharina
A1  - Bégard, Séverine
A1  - Delacourte, André
A1  - Bertrand, Philippe
A1  - Buée, Luc
T1  - p25/Cdk5-mediated retinoblastoma phosphorylation is an early event in neuronal cell death
T2  - Journal of Cell Science
N2  - In large models of neuronal cell death, there is a tight correlation between Cdk5 deregulation and cell-cycle dysfunction. However, pathways that link Cdk5 to the cell cycle during neuronal death are still unclear. We have investigated the molecular events that precede p25/Cdk5-triggered neuronal death using a neuronal cell line that allows inducible p25 expression. In this system, no sign of apoptosis was seen before 24 hours of p25 induction. Thus, at that time, cell-cycle-regulatory proteins were analysed by immunoblotting and some of them showed a significant deregulation. Interestingly, after time-course experiments, the earliest feature correlated with p25 expression was the phosphorylation of the retinoblastoma protein (Rb). Indeed, this phosphorylation was observed 6 hours after p25 induction and was abolished in the presence of a Cdk5 inhibitor, roscovitine, which does not inhibit the usual Rb cyclin-D kinases Cdk4 and Cdk6. Furthermore, analyses of levels and subcellular localization of Cdk-related cyclins did not reveal any change following Cdk5 activation, arguing for a direct effect of Cdk5 activity on Rb protein. This latter result was clearly demonstrated by in vitro kinase assays showing that the p25-Cdk5 complex in our cell system phosphorylates Rb directly without the need for any intermediary kinase activity. Hence, Rb might be an appropriate candidate that connects Cdk5 to cell-cycle deregulation during neuronal cell death.
KW  - Apoptosis
KW  - Cell cycle
KW  - E2F-responsive genes
KW  - SKNSH-SY5Y neuroblastoma cells
Y1  - 2005
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/1968
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-34489
VL  - 118
SP  - 1291
EP  - 1298
ER  -