SUMMARY
Pereda PAL. [Functional study of mutant prion proteins in ligation
domain STI1 and vitronectin]. São Paulo; 2007. [Dissertação de Mestrado-
Fundação Antônio Prudente].
The cellular prion protein (PrP
C
) is a normal isoform of the infectious protein
denominated prion or PrP
Sc
(scrapie prion protein). The infectious form is
envolved in fatal neurodegenerative disorders, such as Creutzfeldt- Jakob
disease (CJD), Gerstman-Straussler-Scheinker syndrome (GSS) and Fatal-
Familial- Insomnia (FFI) in humans, or scrapie and bovine spongiform
encephalopathy (BSE) in animals. Recently, our group characterized two
ligands that interact with PrP
C
through 105-128 aminoacids domain. The first
ligand, STI1 protein (Stress-Inducible-Protein 1), a co-chaperone, binds PrP
C
at the residues 113-128 promoting neuritogenesis and neuroprotection
through distintic signaling pathway. Moreover, PrP
C
-STI1 interaction is
involved in the Glioma cellular proliferation. The second ligand, Vitronectin
(Vn), an extracellular matrix protein, interacts with PrP
C
at the aminoacids
105-119 modulating the axonal growth. PrP
C
mutations at codons Pro102Leu
and Ala117Val (corresponding to aminoacids 101, 104 and 116 in mice
sequence) represents the STI1 and VN binding sites in the PrP
C
molecule
and are associated to Gerstmann-Straussler-Scheinker syndrome (GSS), an
hereditary prion disease. Interestingly, transgenic mice expressing high
levels of PrP
C
mutant (Pro101Leu) showed spontaneous neurodegeneration,
while its expression in basal level causes more susceptibility the PrP
Sc
. On
the other hand, PrP
C
mutation Ala117Val produces a PrP
C
transmembrane
form that does not cause neither deposition of PrP
Sc
nor infection. Taken
together, these data suggest that PrP
C
mutation might be associated to PrP
C
loss-of-function. The modulation of PrP
C
interaction with STI1 and Vitronectin
can still play a relevant role in other human disease related to proliferation
and cellular death, like cancer. Indeed, it is relevant to know the role of the