Protein Information

Name alpha tubulin
Synonyms Alpha tubulin ubiquitous; Tubulin K alpha 1; Tubulin alpha ubiquitous chain; K alpha 1; K ALPHA 1 protein; alpha tubulin; K alpha 1s; K ALPHA 1 proteins…

Compound Information

Name benomyl
CAS

Reference List

PubMed Abstract RScore(About this table)
8601474 Willins DA, Xiang X, Morris NR: An alpha tubulin mutation suppresses nuclear migration mutations in Aspergillus nidulans. Genetics. 1995 Dec;141(4):1287-98.

The mutation alters microtubule staining and confers sensitivity to cold and benomyl, two treatments that destabilize microtubules.
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3294100 Stearns T, Botstein D: Unlinked noncomplementation: isolation of new conditional-lethal mutations in each of the tubulin genes of Saccharomyces cerevisiae. Genetics. 1988 Jun;119(2):249-60.

The unlinked mutation was shown to be a conditional-lethal allele of the major alpha-tubulin-encoding gene (TUB1) and represents the first such mutation in that gene.
The tub1-1 mutation itself causes a cold-sensitive cell-cycle arrest, and confers supersensitivity to the antimicrotubule drug benomyl.
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15031428 Badin-Larcon AC, Boscheron C, Soleilhac JM, Piel M, Mann C, Denarier E, Fourest-Lieuvin A, Lafanechere L, Bornens M, Job D: Suppression of nuclear oscillations in Saccharomyces cerevisiae expressing Glu tubulin. Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5577-82. Epub 2004 Mar 18.


In most eukaryotic cells, the C-terminal amino acid of alpha-tubulin is aromatic (Tyr in mammals and Phe in Saccharomyces cerevisiae) and is preceded by two glutamate residues.
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3066684 Schatz PJ, Solomon F, Botstein D: Isolation and characterization of conditional-lethal mutations in the TUB1 alpha-tubulin gene of the yeast Saccharomyces cerevisiae. Genetics. 1988 Nov;120(3):681-95.

Greater than 90% of the mutants examined were hypersensitive to the antimicrotubule drug benomyl.
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3302605 Oakley BR, Oakley CE, Rinehart JE: Conditionally lethal tubA alpha-tubulin mutations in Aspergillus nidulans. Mol Gen Genet. 1987 Jun;208(1-2):135-44.

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1936991 Kirk KE, Morris NR: The tubB alpha-tubulin gene is essential for sexual development in Aspergillus nidulans. Genes Dev. 1991 Nov;5(11):2014-23.

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19099300 Koo BS, Park H, Kalme S, Park HY, Han JW, Yeo YS, Yoon SH, Kim SJ, Lee CM, Yoon MY: Alpha- and beta-tubulin from Phytophthora capsici KACC 40483: molecular cloning, biochemical characterization, and antimicrotubule screening. Appl Microbiol Biotechnol. 2009 Mar;82(3):513-24. Epub 2008 Dec 20.

The recombinant alpha- and beta-tubulin genes were expressed in Escherichia coli BL21 (DE3), purified under denaturing conditions, and average yields were 3.38-4.5 mg of alpha-tubulin and 2.89-4.0 mg of beta-tubulin, each from 1-l culture.
Benomyl inhibited polymerization with half-maximal inhibition (IC (50)) = 468 +/- 20 microM.
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12802085 Ovechkina Y, Maddox P, Oakley CE, Xiang X, Osmani SA, Salmon ED, Oakley BR: Spindle formation in Aspergillus is coupled to tubulin movement into the nucleus. Mol Biol Cell. 2003 May;14(5):2192-200. Epub 2003 Feb 6.

First, we have used benomyl to disassemble microtubules and create a pool of free tubulin that can be readily observed by immunofluorescence.
Second, we have observed a green fluorescent protein/alpha-tubulin fusion in living cells by time-lapse spinning-disk confocal microscopy.
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11361335 Ghosh SK, Poddar A, Hajra S, Sanyal K, Sinha P: The IML3/MCM19 gene of Saccharomyces cerevisiae is required for a kinetochore-related process during chromosome segregation. Mol Genet Genomics. 2001 Apr;265(2):249-57.

The mutant cells show defective kinetochore function as judged by three criteria-- relaxation of the transcriptional block normally associated with a CEN box, stable maintenance of a dicentric plasmid in mutant cells, and mild sensitivity to the antimicrotubule drug benomyl.
However, the mcm19 null mutation conferred growth defects in the presence of a mutation in the TUB1 gene coding for alpha-tubulin.
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6341617 Oakley BR: Conditionally lethal tubulin mutations of Aspergillus nidulans. J Submicrosc Cytol. 1983 Jan;15(1):363-6.

In the filamentous fungus Aspergillus nidulans it has been possible to isolate heat-sensitive beta-tubulin mutations by isolating mutants resistant to the anti-microtubule agent benomyl and screening these mutants for heat sensitivity.
It has also been possible to isolate alpha-tubulin mutations, new beta-tubulin mutations and mutations in other genes whose products are likely to interact with beta tubulin as revertants of heat-sensitive beta-tubulin mutations.
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7020758 Kilmartin JV: Purification of yeast tubulin by self-assembly in vitro. Biochemistry. 1981 Jun 9;20(12):3629-33.

The yeast tubulin subunits comigrate with the brain alpha-tubulin subunit on one-dimensional sodium dodecyl sulfate gel electrophoresis.
The in vitro yeast tubulin assembly is inhibited by the fungicide methyl N-(benzimidazol-2-yl) carbamate, the active component of benomyl, whereas in vitro brain 6S tubulin assembly is resistant.
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9398684 Schwartz K, Richards K, Botstein D: BIM1 encodes a microtubule-binding protein in yeast. Mol Biol Cell. 1997 Dec;8(12):2677-91.

A previously uncharacterized yeast gene (YER016w) that we have named BIM1 (binding to microtubules) was obtained from a two-hybrid screen of a yeast cDNA library using as bait the entire coding sequence of TUB1 (encoding alpha-tubulin).
Deletion of BIM1 results in a strong bilateral karyogamy defect, hypersensitivity to benomyl, and aberrant spindle behavior, all phenotypes associated with mutations affecting microtubules in yeast, and inviability at extreme temperatures (i.e., >/=37 degrees C or
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19394244 Koo BS, Kalme S, Yeo SH, Lee SJ, Yoon MY: Molecular cloning and biochemical characterization of alpha- and beta-tubulin from potato plants (Solanum tuberosum L.). Plant Physiol Biochem. 2009 Sep;47(9):761-8. Epub 2009 Apr 9.

Solanum tuberosum (Stub) alpha-tubulin and beta-tubulin were predicted to encode 449 and 451 amino acid long proteins with molecular masses of 57 kDa and 60 kDa, respectively.
The amino acids, His6, Glu198, and Phe170 involved in benomyl sensitivity were conserved in Stub tubulin.
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11686676 Takano Y, Oshiro E, Okuno T: Microtubule dynamics during infection-related morphogenesis of Colletotrichum lagenarium. Fungal Genet Biol. 2001 Nov;34(2):107-21.

Two alpha-tubulin genes of C. lagenarium were isolated, and GFP-alpha-tubulin protein was expressed in this fungus.
The strain expressing the fusion protein formed fluorescent filaments that were disrupted by a microtubule-depolymerizing drug, benomyl, demonstrating successful visualization of microtubules.
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13680156 Shields CM, Taylor R, Nazarenus T, Cheatle J, Hou A, Tapprich A, Haifley A, Atkin AL: Saccharomyces cerevisiae Ats1p interacts with Nap1p, a cytoplasmic protein that controls bud morphogenesis. Curr Genet. 2003 Dec;44(4):184-94. Epub 2003 Sep 13.

Saccharomyces cerevisiae ATS1 (alpha-tubulin suppressor 1) was originally identified as a high-copy suppressor of class two alpha-tubulin mutations and was proposed to have a regulatory role in coordinating the microtubule state with the cell cycle.
Deletion of ATS1 partially suppresses the elongated bud morphology and benomyl resistance of nap1Delta mutants.
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12490716 O'Keefe RT: Mutations in U5 snRNA loop 1 influence the splicing of different genes in vivo. Nucleic Acids Res. 2002 Dec 15;30(24):5476-84.


The cell cycle arrest is likely attributed to inefficient splicing of alpha-tubulin pre-mRNA in one mutant and actin pre-mRNA in another.
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6210290 Weatherbee JA, Morris NR: Aspergillus contains multiple tubulin genes. J Biol Chem. 1984 Dec 25;259(24):15452-9.

Previous work with benomyl-resistant mutants of Aspergillus nidulans has demonstrated that the benA locus is a structural gene for beta-tubulin.
Similar techniques have also been applied to a mutant showing altered alpha-tubulins to confirm and modify earlier observations suggesting that at least two structural genes for alpha-tubulins are also present.
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2969337 That TC, Rossier C, Barja F, Turian G, Roos UP: Induction of multiple germ tubes in Neurospora crassa by antitubulin agents. Eur J Cell Biol. 1988 Apr;46(1):68-79.

The microtubule (MT) cytoskeleton of N. crassa could be revealed by indirect immunofluorescence with the monoclonal antibody YOL 1/34 directed against yeast alpha-tubulin.
The antitubulin fungicide benomyl suppressed the linear growth of Neurospora crassa wild type strain St.
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19761543 Ptak C, Anderson AM, Scott RJ, Van de Vosse D, Rogers RS, Sydorskyy Y, Aitchison JD, Wozniak RW: A role for the karyopherin Kap123p in microtubule stability. Traffic. 2009 Nov;10(11):1619-34. Epub 2009 Aug 22.


In support of this idea, we demonstrated genetic interactions between the kap123Delta mutation and mutated alleles of genes encoding alpha-tubulins and factors controlling microtubule dynamics.
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12215672 Correa LM, Nakai M, Strandgaard CS, Hess RA, Miller MG: Microtubules of the mouse testis exhibit differential sensitivity to the microtubule disruptors Carbendazim and colchicine. Toxicol Sci. 2002 Sep;69(1):175-82.


The testicular toxicant benomyl and its metabolite, carbendazim cause reproductive damage to the rat, an early sign of which is sloughing of germ cells with associated Sertoli cell fragments.
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9463374 Geissler S, Siegers K, Schiebel E: A novel protein complex promoting formation of functional alpha- and gamma-tubulin. EMBO J. 1998 Feb 16;17(4):952-66.

The Gim proteins have one function related to alpha-tubulin and another to Tub4p, supported by the finding that the benomyl super-sensitivity is caused by a reduced level of alpha-tubulin while the synthetic lethality with tub4-1 is not.
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11679072 Requena N, Alberti-Segui C, Winzenburg E, Horn C, Schliwa M, Philippsen P, Liese R, Fischer R: Genetic evidence for a microtubule-destabilizing effect of conventional kinesin and analysis of its consequences for the control of nuclear distribution in Aspergillus nidulans. Mol Microbiol. 2001 Oct;42(1):121-32.

In addition, kinesin-deficient strains were less sensitive to the microtubule destabilizing drug benomyl, and disruption of conventional kinesin suppressed the cold sensitivity of an alpha-tubulin mutation (tubA4).
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12711678 Chawla G, Sapra AK, Surana U, Vijayraghavan U: Dependence of pre-mRNA introns on PRP17, a non-essential splicing factor: implications for efficient progression through cell cycle transitions. Nucleic Acids Res. 2003 May 1;31(9):2333-43.

Reduced levels of alpha-tubulin protein, a mitotic spindle component, underlie the benomyl sensitivity of prp17 mutants and possibly their G (2)/M arrest.
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9128252 Saunders W, Hornack D, Lengyel V, Deng C: The Saccharomyces cerevisiae kinesin-related motor Kar3p acts at preanaphase spindle poles to limit the number and length of cytoplasmic microtubules. J Cell Biol. 1997 Apr 21;137(2):417-31.

Addition of the microtubule polymerization inhibitors nocodazol or benomyl to the medium or deletion of the nonessential alpha-tubulin TUB3 gene can mostly correct the abnormal microtubule arrays and other growth defects of kar3 mutants, suggesting that these phenotypes result from excessive microtubule polymerization.
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12937270 Wright AJ, Hunter CP: Mutations in a beta-tubulin disrupt spindle orientation and microtubule dynamics in the early Caenorhabditis elegans embryo. Mol Biol Cell. 2003 Nov;14(11):4512-25. Epub 2003 Aug 22.

Both complementing alleles have distinct effects on microtubule dynamics and show allele-specific interactions with the two embryonically expressed alpha-tubulins: One of the alleles causes microtubules to be cold stable and resistant to the microtubule-depolymerizing drug benomyl, whereas the other causes cell cycle-specific defects in microtubule polymerization.
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10793159 Richards KL, Anders KR, Nogales E, Schwartz K, Downing KH, Botstein D: Structure-function relationships in yeast tubulins. . Mol Biol Cell. 2000 May;11(5):1887-903.

Many of the most benomyl-sensitive tub1 alleles were synthetically lethal in combination with tub3Delta, supporting the idea that benomyl supersensitivity is a rough measure of microtubule instability and/or insufficiency in the amount of alpha-tubulin.
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15548594 Horio T, Oakley BR: The role of microtubules in rapid hyphal tip growth of Aspergillus nidulans. Mol Biol Cell. 2005 Feb;16(2):918-26. Epub 2004 Nov 17.

To define the role of microtubules in tip growth, we used time-lapse microscopy to measure tip growth rates in germlings of A. nidulans and in multinucleate hyphal tip cells, and we used a green fluorescent protein-alpha-tubulin fusion to observe the effects of the antimicrotubule agent benomyl.
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2691873 Takahashi M, Kobayashi H, Iwasaki S: Rhizoxin resistant mutants with an altered beta-tubulin gene in Aspergillus nidulans. Mol Gen Genet. 1989 Dec;220(1):53-9.

Mutants of A. nidulans, benA10 which is a benomyl resistant beta-tubulin gene mutant and tubA1 which is a benomyl supersensitive alpha-tubulin gene mutant, were both sensitive to rhizoxin and ansamitocin P-3 to the same extent as wild-type strains.
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11553707 Caron JM, Vega LR, Fleming J, Bishop R, Solomon F: Single site alpha-tubulin mutation affects astral microtubules and nuclear positioning during anaphase in Saccharomyces cerevisiae: possible role for palmitoylation of alpha-tubulin. Mol Biol Cell. 2001 Sep;12(9):2672-87.

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8336695 Kirk KE, Morris NR: Either alpha-tubulin isogene product is sufficient for microtubule function during all stages of growth and differentiation in Aspergillus nidulans. Mol Cell Biol. 1993 Aug;13(8):4465-76.

In a reciprocal set of experiments, we examined whether upregulation of tubB can complement the tubA4 mutation, which causes supersensitivity to benomyl during vegetative growth.
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7622604 Guenette S, Magendantz M, Solomon F: Suppression of a conditional mutation in alpha-tubulin by overexpression of two checkpoint genes. J Cell Sci. 1995 Mar;108 ( Pt 3):1195-204.

Excess BUB3 rescues both the loss of viability and microtubule defects but not the benomyl supersensitivity associated with tub1-729.
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17307817 Sweet TJ, Boyer B, Hu W, Baker KE, Coller J: Microtubule disruption stimulates P-body formation. RNA. 2007 Apr;13(4):493-502. Epub 2007 Feb 16.

First, we demonstrate that disruption of microtubules by treatment with the drug benomyl leads to aggregation of P-body components.
Consistent with this finding, we also demonstrate that disruption of microtubules by a temperature-sensitive allele of the major alpha tubulin, TUB1 (tub1-724) stimulates P-body formation.
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3540600 Schatz PJ, Solomon F, Botstein D: Genetically essential and nonessential alpha-tubulin genes specify functionally interchangeable proteins. Mol Cell Biol. 1986 Nov;6(11):3722-33.

Null alleles of TUB3, however, did cause several phenotypes, including hypersensitivity to the antimicrotubule drug benomyl and poor spore viability.
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