Linked Life Data

16120615

Source:http://linkedlifedata.com/resource/pubmed/id/16120615

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
43
pubmed:dateCreated
2005-10-24
pubmed:abstractText
erg26-1ts cells harbor defects in the 4alpha-carboxysterol-C3 dehydrogenase activity necessary for conversion of 4,4-dimethylzymosterol to zymosterol. Mutant cells accumulate toxic 4-carboxysterols and are inviable at high temperature. A genetic screen aimed at cloning recessive mutations remediating the temperature sensitive growth defect has resulted in the isolation of four complementation groups, ets1-4 (erg26-1ts temperature sensitive suppressor). We describe the characterization of ets1-1 and ets2-1. Gas chromatography/mass spectrometry analyses demonstrate that erg26-1ts ets1-1 and erg26-1ts ets2-1 cells do not accumulate 4-carboxysterols, rather these cells have increased levels of squalene and squalene epoxide, respectively. ets1-1 and ets2-1 cells accumulate these same sterol intermediates. Chromosomal integration of ERG1 ERG7 at their loci in erg26-1ts ets1-1 and erg26-1ts and ets2-1 mutants, respectively, results in the loss of accumulation of squalene and squalene epoxide, re-accumulation of 4-carboxysterols and cell inviability at high temperature. Enzymatic assays demonstrate that mutants harboring the ets1-1 allele have decreased squalene epoxidase activity, while those containing the ets2-1 allele show weakened oxidosqualene cyclase activity. Thus, ETS1 and ETS2 are allelic to ERG1 and ERG7, respectively. We have mapped mutations within the erg1-1/ets1-1 (G247D) and erg7-1/ets2-1 (D530N, V615E) alleles that suppress the inviability of erg26-1ts at high temperature, and cause accumulation of sterol intermediates and decreased enzymatic activities. Finally using erg1-1 and erg7-1 mutant strains, we demonstrate that the expression of the ERG25/26/27 genes required for zymosterol biosynthesis are coordinately transcriptionally regulated, along with ERG1 and ERG7, in response to blocks in sterol biosynthesis. Transcriptional regulation requires the transcription factors, Upc2p and Ecm22p.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
280
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
35904-13
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16120615-Alleles, pubmed-meshheading:16120615-Blotting, Northern, pubmed-meshheading:16120615-Blotting, Western, pubmed-meshheading:16120615-Cell Proliferation, pubmed-meshheading:16120615-Cholesterol, pubmed-meshheading:16120615-Dose-Response Relationship, Drug, pubmed-meshheading:16120615-Gas Chromatography-Mass Spectrometry, pubmed-meshheading:16120615-Gene Expression Regulation, Fungal, pubmed-meshheading:16120615-Genetic Complementation Test, pubmed-meshheading:16120615-Lac Operon, pubmed-meshheading:16120615-Models, Biological, pubmed-meshheading:16120615-Mutation, pubmed-meshheading:16120615-RNA, Messenger, pubmed-meshheading:16120615-Saccharomyces cerevisiae, pubmed-meshheading:16120615-Signal Transduction, pubmed-meshheading:16120615-Squalene, pubmed-meshheading:16120615-Sterols, pubmed-meshheading:16120615-Temperature, pubmed-meshheading:16120615-Transcription, Genetic, pubmed-meshheading:16120615-beta-Galactosidase
pubmed:year
2005
pubmed:articleTitle
Characterizing sterol defect suppressors uncovers a novel transcriptional signaling pathway regulating zymosterol biosynthesis.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, N.I.H., Extramural