Abstract
The prion protein (PrPC) plays major roles in cellular functions by binding to diverse proteins, forming multi-protein complexes and organizing signaling platforms. These protein complexes need to be better evaluated at molecular and cellular level in order to understand how PrPC associations trigger different cellular signals. PrPC association with Stress-inducible protein 1 or its human homolog Hop (STI1/Hop), which is secreted by astrocytes, promotes neuronal and glial survival and differentiation in vitro, modulates the proliferation of neural stem cells and tumor cells in culture and supports immunological processes. STI1/Hop performs neurotrophic activities and the molecular mechanisms, in particular post-translation modifications, associated with the secretion and regulation of this protein are unknown and need to be approached. It is also a major challenge to identify the functions of STI1/Hop in vivo by using conditional and constitutive STI1/Hop knockout mice, which have been recently generated by our group. Due to its positive role in cell survival (particulary in neurons) and proliferation the complex PrPC-STI1/Hop is a relevant therapeutic target. Its in vivo role in the biology or adult stem cells, in neuroprotection in injury models such as ischemia and radiotherapy, in the proliferation of tumor cells as well as in immunological mechanisms will be largely explored. (AU)
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