Disease relevance of YRB1

• We show here, using all recombinant yeast proteins expressed in Escherichia coli, that karyopherin beta binds to Ran-GTP and inhibits GTP hydrolysis stimulated by RanGAP (the Ran-specific GTPase activating protein) [1].
• Cells deleted for CST20 were less virulent in a mouse model for systemic candidiasis [2].

High impact information on YRB1

• These data indicate that Yrb1p functions with Gsp1p and suggest that together they can control transport of macromolecules across the nuclear envelope [3].
• Mutants in a yeast Ran binding protein are defective in nuclear transport [3].
• The CST20 gene of Candida albicans was cloned by functional complementation of a deletion of the STE20 gene in Saccharomyces cerevisiae [2].
• The Candida heterozygotes CST20/cst20 and HST7/hst7 are also defective in hyphal formation [4].
• Yeast Ran-binding protein 1 (Yrb1) shuttles between the nucleus and cytoplasm and is exported from the nucleus via a CRM1 (XPO1)-dependent pathway [5].

Biological context of YRB1

• Mutations in the YRB1 gene encoding yeast ran-binding-protein-1 that impair nucleocytoplasmic transport and suppress yeast mating defects [6].
• Both mutations result in single amino acid substitutions of evolutionarily conserved residues (A91D and R127K, respectively) in the Ran-binding domain of Yrb1 [6].
• We identified two temperature-sensitive (ts) mutations in the essential gene, YRB1, which encodes the yeast homolog of Ran-binding-protein-1 (RanBP1), a known coregulator of the Ran GTPase cycle [6].
• Thus, Yrb1p is crucial for efficient APC- and SCF-mediated proteolysis of important cell cycle regulatory proteins [7].
• Depletion of Yrb1p results in the accumulation of unbudded G(1) cells and of cells arrested in mitosis implying a function of Yrb1p in the G(1)/S transition and in the progression through mitosis [7].

Anatomical context of YRB1

• Yrb1p is located in the cytosol whereas Nup2p is nuclear [8].
• Mutation of one of these, YRB1, results in defects in transport of macromolecules across the nuclear envelope (Schlenstedt, G., Wong, D. H., Koepp, D. M., and Silver, P. A. (1995) EMBO J. 14, 5367-5378) [9].
• In addition to its role in nucleocytoplasmic transport of macromolecules, YRB1/RanBP1 could be involved in the regulation of microtubules structure and dynamics [10].
• This gene encodes an essential protein that shares homology with the mammalian protein RanBP1 and the protein encoded by the Saccharomyces cerevisiae gene YRB1 and contains a peptide motif present in several proteins found within the nuclear pore complex [11].

Associations of YRB1 with chemical compounds

• Nuclear export of Yrb1, however, is insensitive towards leptomycin B, suggesting a novel type of substrate recognition between Yrb1 and Xpo1 [5].
• Export from the nucleus requires Xpo1p, but Yrb1p does not contain a leucine-rich NES [12].
• The Ran binding protein RanBPM interacts with Axl and Sky receptor tyrosine kinases [13].

Physical interactions of YRB1

• YRB2 encodes a protein containing a Ran-binding motif similar to that found in Yrb1p and Nup2p [8].
• A mutation in the highly conserved Ran binding region of Yrb1p reduces its ability to interact with Gsp1p [3].
• Ran-binding protein 1 (RanBP1) forms a ternary complex with Ran and karyopherin beta and reduces Ran GTPase-activating protein (RanGAP) inhibition by karyopherin beta [14].

Regulatory relationships of YRB1

• While overproduction of Yrb1p inhibited the growth of a mutant possessing a PRP20 mutation (srm1-1) and suppressed the rna1-1 mutation, overproduction of Yrb2p showed no effect on the growth of these mutants [8].

Other interactions of YRB1

• Yrb1p did not inhibit the Mog1p-stimulated nucleotide release from GTP-Gsp1DeltaC [15].
• In contrast to Yrb1p, Yrb30p does not coactivate but inhibits RanGAP1(Rna1p)-mediated GTP hydrolysis on Ran, like the karyopherins [16].
• In contrast to other yrb1 alleles, the new mutation (yrb1-21) does not cause visible defects in import of nuclear proteins Npl3p, histone H2B, or beta-galactosidase fused to a nuclear localization signal [17].
• The same effect is achieved for the entire Gcn4p in a yrb1 yeast mutant strain impaired in the nuclear import machinery [18].

Analytical, diagnostic and therapeutic context of YRB1

• Molecular cloning of CaYRB1, the Candida albicans RanBP1/YRB1 homologue [10].

References