The prion protein interacts with Bcl-2 and Bax proteins

The function of the normal cellular human prion protein (PrPC), a highly expressed protein of the brain, is presently unclear. Based on the amino acid sequence homology between PrPC, Bcl-2, and Bax proteins, we propose that PrPC may be implicated in modulating neuronal survival and death as a member of the Bcl-2 family of proteins. The present study investigates interactions between human PrPC, Bcl-2, and Bax in human primary foetal neurons as well as in, human foetal and adult brains by crosslinking and co-immunoprecipitation. The PrPC-Bcl-2 interaction was also tested by the yeast-two-hybrid system. Results indicate an interaction between PrPC and Bcl-2 as well as PrPC and Bax in vivo and in vitro. In addition, the expression levels of PrPC, Bcl-2, and Bax were studied in the cerebellum of human foetal and adult brain. Results show that the levels of Bcl-2 and Bax decrease with age whereas the levels of PrPC increase. In the aging central nervous system, PrPC may functionally replace Bcl-2 or Bax. Overexpression or different modifications of PrPC such as conformational change and mutations may disrupt the protein-protein interactions between PrPC, Bcl-2, and Bax. If PrPC-Bcl-2/Bax interactions function in neuronal survival, disruption of these interactions could explain the underlying molecular mechanism of neuronal death in prion diseases. (Abstract shortened by UMI.)...