A missense mutation in Caenorhabditis elegans prohibitin 2 confers an atypical multidrug resistance.

A missense mutation in Caenorhabditis elegans prohibitin 2 confers an atypical multidrug resistance. Research Abstract Details 

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A missense mutation in Caenorhabditis elegans prohibitin 2 confers an atypical multidrug resistance. Abstract Text:

Iryna Zubovych,Thomas Doundoulakis,Patrick G Harran,Michael G Roth,

Hemiasterlin is a potent antimitotic peptide that interferes with microtubule dynamics at picomolar concentrations in cell culture. The molecule largely eludes P glycoprotein-mediated drug efflux, and an analog is currently being evaluated in clinical trials as cancer chemotherapy. From a nonclonal genetic screen in Caenorhabditis elegans we isolated eight independent mutants resistant to a synthetic hemiasterlin analog. In one recessive mutant, phb-2(ad2154), a point mutation in prohibitin 2 (E130K) protects worms from drug-induced injury. Data indicate that direct binding of hemiasterlin to prohibitin 2 is unlikely. In fact, C. elegans phb-2(ad2154) was also found to be resistant to numerous other drugs that bind tubulin and to camptothecin, yet this mutant was sensitive to nocodazole and phalloidin. Thus, prohibitin 2 is implicated in a previously uncharacterized pathway of multidrug resistance.

A missense mutation in Caenorhabditis elegans prohibitin 2 confers an atypical multidrug resistance. Publishing Authors By Initials

I Zubovych,T Doundoulakis,PG Harran,MG Roth,

For similar chemical actions and uses: pharmacologic actions: molecular mechanisms of pharmacological action: mitosis modulators: antimitotic agents: tubulin modulators research abstracts see: chemical actions and uses: pharmacologic actions: molecular mechanisms of pharmacological action: mitosis modulators: antimitotic agents: tubulin modulators research

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A missense mutation in Caenorhabditis elegans prohibitin 2 confers an atypical multidrug resistance. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Proceedings of the National Academy of Sciences of

VOLUME: 103

Page Numbers: 15523-8

Journal Abbreviation: Proc. Natl. Acad. Sci. U.S.A.

ISSN: 0027-8424

DAY: 10

MONTH: 10

YEAR: 2006

A missense mutation in Caenorhabditis elegans prohibitin 2 confers an atypical multidrug resistance. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7505876

A missense mutation in Caenorhabditis elegans prohibitin 2 confers an atypical multidrug resistance. Keywords Mesh Terms:

KEYWORDS: Tubulin Modulators

MESH TERMS: pharmacology

Chemical & Substance for Abstract: A missense mutation in Caenorhabditis elegans prohibitin 2 confers an atypical multidrug resistance. Information

Substance Name: Nocodazole

Registry Number: 31430-18-9

Grant and Affiliation Information for A missense mutation in Caenorhabditis elegans prohibitin 2 confers an atypical multidrug resistance.

AFFILIATION: Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9038, USA.

Country: United States

AGENCY: United States NCI

GRANT: P01CA95471

ACRONYM: CA

MEDLINETA: Proc Natl Acad Sci U S A

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