Linked Life Data

15709760

Source:http://linkedlifedata.com/resource/pubmed/id/15709760

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2005-2-15
pubmed:abstractText
Pokeweed antiviral protein (PAP) is a single-chain ribosome inactivating protein (RIP) that binds to ribosomes and depurinates the highly conserved alpha-sarcin/ricin loop (SRL) of the large subunit rRNA. Catalytic depurination of a specific adenine has been proposed to result in translation arrest and cytotoxicity. Here, we show that both precursor and mature forms of PAP are localized in the endoplasmic reticulum (ER) in yeast. The mature form is retro-translocated from the ER into the cytosol where it escapes degradation unlike the other substrates of the retro-translocation pathway. A mutation of a highly conserved asparagine residue at position 70 (N70A) delays ribosome depurination and the onset of translation arrest. The ribosomes are eventually depurinated, yet cytotoxicity and loss of viability are markedly absent. Analysis of the variant protein, N70A, does not reveal any decrease in the rate of synthesis, subcellular localization, or the rate of transport into the cytosol. N70A destabilizes its own mRNA, binds to cap, and blocks cap dependent translation, as previously reported for the wild-type PAP. However, it cannot depurinate ribosomes in a translation-independent manner. These results demonstrate that N70 near the active-site pocket is required for depurination of cytosolic ribosomes but not for cap binding or mRNA destabilization, indicating that the activity of PAP on capped RNA can be uncoupled from its activity on rRNA. These findings suggest that the altered active site of PAP might accommodate a narrower range of substrates, thus reducing ribotoxicity while maintaining potential therapeutic benefits.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2478-90
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:15709760-Alanine, pubmed-meshheading:15709760-Amino Acid Sequence, pubmed-meshheading:15709760-Amino Acid Substitution, pubmed-meshheading:15709760-Asparagine, pubmed-meshheading:15709760-Binding Sites, pubmed-meshheading:15709760-Cell Membrane, pubmed-meshheading:15709760-Conserved Sequence, pubmed-meshheading:15709760-Cytosol, pubmed-meshheading:15709760-Endoplasmic Reticulum, pubmed-meshheading:15709760-Molecular Sequence Data, pubmed-meshheading:15709760-N-Glycosyl Hydrolases, pubmed-meshheading:15709760-Phytolacca, pubmed-meshheading:15709760-Plant Proteins, pubmed-meshheading:15709760-Protein Synthesis Inhibitors, pubmed-meshheading:15709760-Protein Transport, pubmed-meshheading:15709760-RNA Caps, pubmed-meshheading:15709760-Ribosome Inactivating Proteins, Type 1, pubmed-meshheading:15709760-Ribosomes, pubmed-meshheading:15709760-Saccharomyces cerevisiae
pubmed:year
2005
pubmed:articleTitle
Evidence for retro-translocation of pokeweed antiviral protein from endoplasmic reticulum into cytosol and separation of its activity on ribosomes from its activity on capped RNA.
pubmed:affiliation
Graduate Program in Microbiology and Molecular Genetics, Rutgers University, New Brunswick, New Jersey 08901-8520, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.