Disease relevance of TUB2

• Truncation of the carboxy-terminal domain of yeast beta-tubulin causes temperature-sensitive growth and hypersensitivity to antimitotic drugs [1].
• All of the observed regulation of levels of tubulin can be explained as a response to toxicity associated with excess tubulin proteins, especially if beta-tubulin is much more toxic than alpha-tubulin [2].
• Further comparisons between the P. carinii beta-tubulin and those of fungal beta-tubulins resistant to benomyl, a beta-tubulin-binding drug, indicate a difference which may be exploited in the development of a new drug therapy for P. carinii pneumonitis [3].
• Starting with 7.7 mg of a beta-tubulin isolated from myxamoebae of the slime mould Physarum polycephalum, 90% of the sequence has been determined by the Edman degradation of peptides generated by cyanogen bromide, trypsin and Staphylococcus aureus protease [4].
• Furthermore, we calculated the correlation coefficients for the cu patterns of the helminth beta-tubulin sequences compared with those of highly expressed genes in organisms such as Escherichia coli and C. elegans [5].

High impact information on TUB2

• At the lateral contacts, a nucleotide-sensitive helix interacts with a loop that contributes to the binding site of taxol in beta-tubulin [6].
• One, RBL2, rescues beta-tubulin lethality as efficiently as does alpha-tubulin [7].
• Rbl2p, a yeast protein that binds to beta-tubulin and participates in microtubule function in vivo [7].
• A chicken-yeast chimeric beta-tubulin DNA was introduced into 3T3 cells using the transfection vector pSV2 [8].
• The fragment was shown to be unique in the yeast genome and to contain the gene for yeast beta-tubulin, since it can complement a benomyl-resistant conditional-lethal mutation [9].

Biological context of TUB2

• We have identified a protein, BAF1, which has two oppositely oriented, partially overlapping binding sites within a symmetrical sequence located midway between and upstream of the divergently transcribed YPT1 and TUB2 genes of the yeast Saccharomyces cerevisiae [10].
• The symmetrical sequence of the YPT1/TUB2 intergene region seems not to be involved in DNA replication but activates transcription in an orientation-independent fashion [10].
• Overexpression of beta-tubulin (TUB2) was lethal: cells arrested in the G2 stage of the cell cycle exhibited an increased frequency of chromosome loss, were devoid of microtubules, and accumulated beta-tubulin in a novel structure [11].
• Impaired core promoter recognition caused by novel yeast TAF145 mutations can be restored by creating a canonical TATA element within the promoter region of the TUB2 gene [12].
• To identify sequences which rendered transcription yTAF145 dependent, we conducted deletion analysis of the TUB2 promoter using a novel mini-CLN2 hybrid gene reporter system [12].

Anatomical context of TUB2

• Despite the essential function of Ppp4c-R2 in microtubule-related processes at centrosomes in higher eukaryotes, S. cerevisiae diploid strains with homozygous deletion of YBL046w and two or one functional copies of the TUB2 gene were viable and no more sensitive to microtubule-depolymerizing drugs than the control strain [13].
• Pac10 null cells show a 30% decrease in the ratio of alpha-tubulin to beta-tubulin [14].
• Microtubules are cytoskeletal organelles composed principally of polymerized alpha beta-tubulin heterodimers [15].
• Cells overproducing only beta-tubulin accumulated fibrous structures associated with the cell membrane, whereas cells overproducing only alpha-tubulin displayed a diffuse signal throughout the cytoplasm [15].
• Previously, we introduced mutations into the S. cerevisiae gene for beta-tubulin that imparted paclitaxel binding to the protein, but the mutant strain was not sensitive to paclitaxel and other microtubule-stabilizing agents, due to the multiple ABC transporters in the membranes of budding yeast [16].

Associations of TUB2 with chemical compounds

• Molecular characterization of four beta-tubulin genes from dinitroaniline susceptible and resistant biotypes of Eleusine indica [17].
• Microtubule dynamics modulated by guanosine triphosphate hydrolysis activity of beta-tubulin [18].
• Specific residues previously implicated in benzimidazole sensitivity were conserved in P. carinii beta-tubulin [19].
• In an electron diffraction model of the tubulin dimer, this sequence comes close to the phosphates of a guanine nucleotide bound in the beta-tubulin exchangeable E site [20].
• We introduced a threonine-to-glycine point mutation at position 143 in the "tubulin signature motif" 140Gly-Gly-Gly-Thr-Gly-Ser-Gly146 of Saccharomyces cerevisiae beta-tubulin [20].

Physical interactions of TUB2

• Residues in the N termini and the loops of the Rbl2 homodimer appear to mediate binding to beta-tubulin [21].

Regulatory relationships of TUB2

• The Arabidopsis TUBULIN-FOLDING COFACTOR A gene is involved in the control of the alpha/beta-tubulin monomer balance [22].
• We find that deletion of PLP1 suppresses toxic beta-tubulin formed by disparate levels of alpha- and beta-tubulin [23].

Other interactions of TUB2

• STU1, a suppressor of a beta-tubulin mutation, encodes a novel and essential component of the yeast mitotic spindle [24].
• The systematic tub1 mutations were placed, along with the comparable set of tub2 mutations previously described, onto a model of the yeast alpha-beta-tubulin dimer based on the three-dimensional structure of bovine tubulin [25].
• Several conditional-lethal mutant alleles of the single-copy Saccharomyces cerevisiae beta-tubulin and actin genes were used to evaluate the roles of microtubules and actin filaments in the pheromone-induced extension of mating projections [26].
• Overexpression of the JSN1 gene in a TUB2 strain causes that strain to become more sensitive to benomyl, a microtubule-destabilizing drug [27].
• We have used computational docking and site-directed mutagenesis to generate a model of the Rbl2-Tub2 complex from the solved structures of these two proteins [21].

Analytical, diagnostic and therapeutic context of TUB2

• We report the cloning and sequence analysis of the yeast BAF1 gene which encodes an abundant protein previously shown to act as a transcription activator in the YPT1-TUB2 intergene region [28].
• Western blots (immunoblots) of H. capsulatum yeast-specific proteins resolved by two-dimensional gel electrophoresis demonstrated a single alpha- and a single beta-tubulin isoform [29].
• Cloning and sequence of a beta-tubulin cDNA from Pneumocystis carinii: possible implications for drug therapy [3].
• On the basis of genomic Southern-blot analysis, we conclude that C. albicans most likely possesses a single beta-tubulin gene [30].
• Polymerase chain reaction (PCR) was utilized to isolate and identify the genes encoding calmodulin, beta-tubulin, DNA polymerase II, and RNA polymerases I, II and III from P. carinii [31].

References