Involvement of cell cycle elements, cyclin-dependent kinases, pRb, and E2Fcenter dot DP, in B-amyloid-induced neuronal death

Citation
A. Giovanni et al., Involvement of cell cycle elements, cyclin-dependent kinases, pRb, and E2Fcenter dot DP, in B-amyloid-induced neuronal death, J BIOL CHEM, 274(27), 1999, pp. 19011-19016
Citations number
42
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
00219258 → ACNP
Volume
274
Issue
27
Year of publication
1999
Pages
19011 - 19016
Database
ISI
SICI code
0021-9258(19990702)274:27<19011:IOCCEC>2.0.ZU;2-R
Abstract
Previous evidence by others has indicated that a variety of cell cycle-rela ted molecules are up-regulated in brains of Alzheimer's disease patients. T he significance of this increase, however, is unclear. Accordingly, we exam ined the obligate nature of cyclin-dependent kinases and select downstream targets of these kinases in death of neurons evoked by B-amyloid (AB) prote in. We present pharmacological and molecular biological evidence that cycli n dependent kinases, in particular Cdk4/6, are required for such neuronal d eath. In addition, we demonstrate that the substrate of Cdk4/6, pRb/ p107, is phosphorylated during AB treatment and that one target of pRb/p107, the E2F.DP complex, is required for AB-evoked neuronal death. These results pro vide evidence that cell cycle elements play a required role in death of neu rons evoked by AB and suggest that these elements play an integral role in Alzheimer's disease-related neuronal death.