@article{bfdf7e95ad5b4d2ca4ebb90df3d1164e,
title = "Cdc2 phosphorylation of BAD links the cell cycle to the cell death machinery",
abstract = "A mechanism that triggers neuronal apoptosis has been characterized. We report that the cell cycle-regulated protein kinase Cdc2 is expressed in postmitotic granule neurons of the developing rat cerebellum and that Cdc2 mediates apoptosis of cerebellar granule neurons upon the suppression of neuronal activity. Cdc2 catalyzes the phosphorylation of the BH3-only protein BAD at a distinct site, serine 128, and thereby induces BAD-mediated apoptosis in primary neurons by opposing growth factor inhibition of the apoptotic effect of BAD. The phosphorylation of BAD serine 128 inhibits the interaction of growth factor-induced serine 136-phosphorylated BAD with 14-3-3 proteins. Our results suggest that a critical component of the cell cycle couples an apoptotic signal to the cell death machinery via a phosphorylation-dependent mechanism that may generally modulate protein-protein interactions.",
author = "Yoshiyuki Konishi and Maria Lehtinen and Nicole Donovan and Azad Bonni",
note = "Funding Information: We thank G. Gill and Y. Shi for critical reading of the manuscript, D. Piscopo and P. Hinds for providing the Cdc2 plasmids, M.-S. Lee and L.-H. Tsai for providing Cdk5 reagents, R. Vallee for the MAP2 antibody, and S. Vasquez for technical assistance. The TAG-1 antibody was obtained from the Developmental Studies Hybridoma Bank (DSHB) under the auspices of the NICHD and maintained by the University of Iowa, Department of Biological Science (Iowa City, IA). This work was supported by a Burroughs Wellcome Career Development Award (A.B.), a Taplin postdoctoral research fellowship (Y.K.), an NSF graduate research fellowship (M.L.), and by an NIH grant to A.B. (R01-NS41021-01). A.B. is the recipient of a fellowship from the Alfred P. Sloan Foundation, a Robert H. Ebert Clinical Scholar Award from the Esther A. and Joseph Klingenstein Fund, an EJLB Foundation award, and a Sidney Kimmel Foundation Award.",
year = "2002",
doi = "10.1016/S1097-2765(02)00524-5",
language = "English",
volume = "9",
pages = "1005--1016",
journal = "Molecular Cell",
issn = "1097-2765",
number = "5",
}