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  • Neuroscience
  • Cell & molecular biology

Published online: 4 June 2008 | doi:10.1038/nchina.2008.130

Neuron survival: A matter of life and death

Jane Qiu

Introduction

Cyclin-dependent kinase 5 (Cdk5), a type of enzyme that regulates the activity of target molecules by tagging phosphate groups onto them, is crucial for inducing cell death in diseased nervous systems. Paradoxically, it is also implicated in the maintenance of survival signals, but the underpinning mechanism is unclear. Nancy Yuk Yu Ip and co-workers at the Hong Kong University of Science and Technology¹ have identified a novel target of Cdk5, which may be responsible for this effect.

The researchers first showed that a reduction in Cdk5 activity led to marked neuronal death in cell culture and adult rats. This was associated with an increased release of cytochrome C — a small heme protein residing in the inner membrane of mitochondria, which are often referred to as the 'cellular power plant'.

Interestingly, Ip and co-workers found that Bcl-2, a protein involved in regulating cytochrome C release and cell survival, turned out to be a novel target for Cdk5. Phosphorylation of Bcl-2 by Cdk5 is necessary for preventing the cell from activating its 'suicide' programmes — apoptosis. By contrast, a Bcl-2 mutant that could not be phosphorylated by Cdk5 was able to induce apoptosis.

In addition, re-introduction of Cdk5 in neurons lacking the protein was able to rescue them from cell death, and this effect was abolished by over-expressing the phosphorylation-deficient Bcl-2 mutant. The researchers hold the opinion that, through its kinase activity, Cdk5 may act as a switch between the pro-apoptotic and anti-apoptotic functions of Bcl-2.

The authors of this work are from:
Department of Biochemistry, Hong Kong University of Science and Technology, Hong Kong, China.

Reference

1. Cheung, Z. H., Gong, K. & Ip, N. Y. Cyclin-dependent kinase 5 supports neuronal survival through phosphorylation of Bcl-2. J. Neurosci. 28, 4872–4877 (2008). | Article | PubMed | ChemPort |