Linked Life Data

12649178

Source:http://linkedlifedata.com/resource/pubmed/id/12649178

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-3-21
pubmed:abstractText
The A549 Taxol-resistant cell lines, A549-T12 and A549-T24, were isolated in our laboratory, and are dependent on Taxol for normal growth. The microtubules in these cells displayed increased dynamicity in the absence of Taxol. In the present study, a heterozygous point mutation in Kalpha1-tubulin was discovered at alpha379 (Ser to Ser/Arg). Although Taxol binds to beta-tubulin in the microtubule, sequencing of beta-tubulin class I did not reveal any mutations. The expression of the alpha-tubulin mutation was demonstrated using high-resolution isoelectric focusing and two-dimensional gel analysis. Both the wild-type and mutant tubulin were expressed in the Taxol-resistant cell lines. The region of alpha-tubulin that encompasses alpha379 is near the COOH terminus that has been proposed as a site of interaction with microtubule-associated protein (MAP) 4 and stathmin, a tubulin-interacting protein. In the Taxol-resistant cells, the active nonphosphorylated form of stathmin was increased approximately 2-fold, whereas the inactive phosphorylated forms were barely detected. The inactive phosphorylated forms of MAP4 were increased in the A549-T12 and A549-T24 cell lines. We hypothesize that these changes in tubulin/MAPs that result in increased microtubule instability may be related to the alpha-tubulin mutation and are compensated for by the stabilizing properties of Taxol.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
63
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1207-13
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12649178-Amino Acid Sequence, pubmed-meshheading:12649178-Antineoplastic Agents, Phytogenic, pubmed-meshheading:12649178-DNA Mutational Analysis, pubmed-meshheading:12649178-Drug Resistance, Neoplasm, pubmed-meshheading:12649178-Humans, pubmed-meshheading:12649178-Microtubule Proteins, pubmed-meshheading:12649178-Microtubule-Associated Proteins, pubmed-meshheading:12649178-Microtubules, pubmed-meshheading:12649178-Molecular Sequence Data, pubmed-meshheading:12649178-Paclitaxel, pubmed-meshheading:12649178-Phosphoproteins, pubmed-meshheading:12649178-Point Mutation, pubmed-meshheading:12649178-Protein Conformation, pubmed-meshheading:12649178-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:12649178-Stathmin, pubmed-meshheading:12649178-Tubulin, pubmed-meshheading:12649178-Tumor Cells, Cultured
pubmed:year
2003
pubmed:articleTitle
Elevated levels of microtubule destabilizing factors in a Taxol-resistant/dependent A549 cell line with an alpha-tubulin mutation.
pubmed:affiliation
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.