Linked Life Data

15490173

Source:http://linkedlifedata.com/resource/pubmed/id/15490173

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2005-3-3
pubmed:abstractText
4-Phenylbutyrate (PB) induces differentiation and is being intensively studied as a treatment for brain, prostate, breast, and hematopoietic cancer. While many different primary targets for PB have been proposed, the mechanism by which it causes cellular differentiation remains unknown. To identify the primary cellular target, we investigated its effects on Saccharomyces cerevisiae and showed that it inhibits tryptophan transport. We show here that PB and sorbic acid induce an ubiquitin-dependent turnover of the tryptophan permease Tat2p. However, the inhibition of transport is not a consequence of the loss of Tat2p, since it also occurs when turnover is prevented by deleting the Tat2p ubiquitination sites. When we tested the effects of PB and other growth inhibitory agents on the growth of amino acid auxotrophs, we found that several auxotrophs are hypersensitive to a number of chemically unrelated agents, including PB and some, but not all, weak acids; and this sensitivity is due to the inhibition of amino acid transport. For the inhibitory weak acids, inhibition is not confined to aromatic amino acid auxotrophs, nor is it a general weak acid stress response, since the degree of inhibition is independent of weak acid hydrophobicity and p Ka. Our results show that diverse agents affect the activity of the Tat2p permease rather than its stability and suggest the hypothesis that the anti-neoplastic action of PB is due to a decrease in the activity of surface receptors or other membrane proteins needed to maintain the transformed state.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0172-8083
pubmed:author
pubmed:issnType
Print
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
256-68
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Activity of the yeast Tat2p tryptophan permease is sensitive to the anti-tumor agent 4-phenylbutyrate.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, 540 E. Canfield Ave, Detroit, MI 48201, USA.
pubmed:publicationType
Journal Article, Comparative Study