Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.108 (TAT)
 2,389 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In humans, familial prion diseases are linked to mutations in the PRNP gene. We have sequenced part of this gene in a large sample of common chimpanzee, Pan troglodytes (n=130 chromosomes). No variation in codons 129 and 219 has been observed: all chimpanzees were homozygous for the Met allele, which in humans increases susceptibility to Creutzfeldt-Jakob disease. We found two sequence variants: one is a synonymous polymorphism unique to the chimpanzee at codon 226, TAC to TAT (Y), with a TAC allele frequency of 80.6%; the other is a non-synonymous change at codon 148 (R148H) that falls in the target epitope for some common commercial antibodies used for prion diagnostics, and is highly conserved across species. The pathogenicity of this mutation is still unknown.
 ...
PMID:Variation of the prion gene in chimpanzees and its implication for prion diseases. 1473 55

Transmissible spongiform encephalopathies, including variant-Creutzfeldt-Jakob disease (vCJD) in humans and bovine spongiform encephalopathies in cattle, are fatal neurodegenerative disorders characterized by protein misfolding of the host cellular prion protein (PrP(C)) to the infectious scrapie form (PrP(Sc)). However, the mechanism that exogenous PrP(Sc) infects cells and where pathologic conversion of PrP(C) to the PrP(Sc) form occurs remains uncertain. Here we report that similar to the mechanism of HIV-1 TAT-mediated peptide transduction, processed mature, full length PrP contains a conserved N-terminal cationic domain that stimulates cellular uptake by lipid raft-dependent, macropinocytosis. Inhibition of macropinocytosis by three independent means prevented cellular uptake of recombinant PrP; however, it did not affect recombinant PrP cell surface association. In addition, fusion of the cationic N-terminal PrP domain to a Cre recombinase reporter protein was sufficient to promote both cellular uptake and escape from the macropinosomes into the cytoplasm. Inhibition of macropinocytosis was sufficient to prevent conversion of PrP(C) to the pathologic PrP(Sc) form in N2a cells exposed to strain RML PrP(Sc) infected brain homogenates, suggesting that a critical determinant of PrP(C) conversion occurs following macropinocytotic internalization and not through mere membrane association. Taken together, these observations provide a cellular mechanism that exogenous pathological PrP(Sc) infects cells by lipid raft dependent, macropinocytosis.
 ...
PMID:Pathologic prion protein infects cells by lipid-raft dependent macropinocytosis. 1939 Jun 57