Cell Biology

Paradoxical Signaling

Science Signaling  25 Mar 2008:
Vol. 1, Issue 12, pp. ec108
DOI: 10.1126/stke.112ec108

In contrast to its role in stimulating DNA synthesis and cell division, the cyclin-dependent kinase CDK1 has been implicated in signaling that leads to cell death in nonproliferating neuronal cells. Yuan et al. present evidence that the CDK1 protein kinase phosphorylates the FOXO1 transcription factor, which leads to the accumulation of FOXO1 in the nucleus and activation of a FOXO1-dependent reporter gene. This conclusion contrasts with previous work, which reported that phosphorylation of FOXO1 by CDK2 caused movement of FOXO1 out of the nucleus and decreased FOXO1-dependent transcription. In proliferating cells, CDK1-induced activation of FOXO1 led to increased expression of the gene encoding another kinase that contributes to regulation of mitosis--polo-like kinase (Plk). These results may lead to better understanding of neuronal degeneration.

Z. Yuan, E. B. E. Becker, P. Merlo, T. Yamada, S. DiBacco, Y. Konishi, E. M. Schaefer, A. Bonni, Activation of FOXO1 by Cdk1 in cycling cells and postmitotic neurons. Science 319, 1665-1668 (2008). [Abstract] [Full Text]