Biosynthesis of prion protein nucleocytoplasmic isoforms by alternative initiation of translation.
J Biol Chem
; 284(5): 2787-2794, 2009 Jan 30.
Article
em En
| MEDLINE
| ID: mdl-19059915
ABSTRACT
The cellular prion protein PrP(C) is synthesized as a family of four distinct forms. Of these, (Cyt)PrP is a minor member that segregates outside of the secretory route and can generate cytotoxic forms. Using signal sequence mutants, we found that (Cyt)PrP is translated from a downstream AUG (coding for Met-8 in human PrP or Met-15 in Syrian hamster PrP). Shortening of the signal sequence dictated the spillage of this isoform into the cytosol, from where it accessed the nucleus or formed insoluble cytosolic aggregates if the proteasome is inhibited. The PrP isoform isolated from the nuclear fractions of cell and brain homogenates was partially SUMO-1-conjugated. Expression of HaPrP(M15) in cells caused an antiproliferative phenotype due to a cell cycle arrest at the G(0)/G(1) phase. The identification of this PrP isoform and its properties provides novel insight into PrP(C) physiological and pathological functions.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Príons
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Núcleo Celular
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Isoformas de Proteínas
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Citoplasma
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article