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First published online March 10, 2005

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Cycle route to cell death

Neuronal cell death is a feature of many neurological disorders, including Alzheimer's. Paradoxically, prior to their death, neurons in the brain (which normally remain in G0 phase) appear to re-enter the cell cycle. One tell-tale sign of cell cycle entry is the inactivating phosphorylation of the retinoblastoma tumour suppressor protein (Rb), which allows the cell cycle to proceed. Under normal circumstances, this is performed by the cyclin-dependent kinases CDK4 and CDK6. Luc Buée and co-workers now demonstrate that, in neuronal cell death, a quite different kinase – CDK5 – could be responsible (see p. 1291). Although related to other CDKs, CDK5 is activated by two non-cyclin proteins: p35 (which also has a cleaved form, p25) and p39. Using cells in which p25 triggers apoptosis, Buée and co-workers show that Rb phosphorylation is an early event. Significantly, they are able to block it with the CDK5 inhibitor roscovitine. This does not inhibit CDK4 or CDK6, and the levels of the cyclins that activate these CDKs do not change. The authors also show that CDK5 can phosphorylate Rb in vitro. They therefore conclude that the kinase could provide a shortcut to cell cycle dysregulation that is crucial for neuronal apoptosis.

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Related articles in JCS:

p25/Cdk5-mediated retinoblastoma phosphorylation is an early event in neuronal cell death

Malika Hamdane, Alexis Bretteville, Anne-Véronique Sambo, Katharina Schindowski, Séverine Bégard, André Delacourte, Philippe Bertrand, and Luc Buée
JCS 2005 118: 1291-1298. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?