Disease relevance of CDC31

• Cdc31p was expressed and purified from Escherichia coli and active for binding calcium [1].

High impact information on CDC31

• A previously reported cdc31 temperature-sensitive allele, which is neither defective in SPB duplication nor Kic1 kinase activation, induces mRNA export defects [2].
• We show that overproduction of a sequence, termed CID, in the carboxy-terminal domain of the nuclear export factor Sac3 titrates Cdc31, causing a dominant-lethal phenotype and a block in spindle pole body (SPB) duplication [2].
• The Saccharomyces cerevisiae centrin, Cdc31p, binds Sfi1p on multiple conserved repeats; both proteins localize to the SPB half-bridge, where the new SPB is assembled [3].
• Like cells containing mutations in two other genes required for this step of SPB duplication (CDC31 and KAR1), mps3-1 mutants arrest with a single unduplicated SPB that lacks an associated half-bridge [4].
• We determined that CDC31 gene function is downstream of DSK2 and KAR1 [5].

Biological context of CDC31

• The high copy number suppressor plasmids contained the wild-type CDC31 gene [6].
• However, the CDC31 alleles also made the cell supersensitive to KAR1 gene dosage, arguing against a simple bypass mechanism of suppression [6].
• Eleven extragenic suppressor mutations mapped to two linkage groups, DSK1 and DSK2 [6].
• We postulate that Cdc31p is required both for SPB duplication and for cell integrity/morphogenesis, and that the integrity/morphogenesis function is mediated through the Kic1p protein kinase [7].
• Molecular cloning studies have recently shown that the cell cycle gene product CDC31, required for spindle pole body duplication, shares 50% sequence homology with centrin (Huang, B., A. Mengersen, and V.D. Lee. 1988. J. Cell Biol. 107:133-140) [8].

Anatomical context of CDC31

• Genetic interactions between CDC31 and KAR1, two genes required for duplication of the microtubule organizing center in Saccharomyces cerevisiae [6].
• Saccharomyces cerevisiae strains bearing temperature-sensitive alleles of the cell division cycle gene CDC31 are specifically defective in duplication of the spindle pole body, the microtubule-organizing center of yeast [9].
• We report here that this isoform specifically reacts with antibodies raised against Saccharomyces cerevisiae Cdc31p and is present, as other centrin isoforms, in the distal lumen of centrioles [10].
• Key steps in spindle pole body duplication are the sequential recruitment of Cdc31p and Spc42p by the nuclear envelope transmembrane protein Msp3p/Nep98p (herein termed Mps3p) [11].

Physical interactions of CDC31

• Using a protein blotting technique, Cdc31p bound to Kar1p in vitro via an essential domain in Kar1p required for SPB duplication (Vallen, E. A., M. A. Hiller, T. Y. Scherson, and M. D. Rose. 1992a. J. Cell Biol. 117:1277-1287) [1].
• Cdc31p was also able to bind to the carboxy terminus of Nuflp/Spc110p, another component of the SPB (Kilmartin, J. V., S. L. Dyos, D. Kershaw, and J. T. Finch. 1993. J. Cell Biol. 123:1175-1184) [12].
• On the basis of comparison with these related proteins, it is evident that the CDC31 gene product has at least two binding sites for Ca2+ and is also homologous with other regions of the calmodulin sequence [9].

Other interactions of CDC31

• The Saccharomyces cerevisiae genes KAR1 and CDC31 are required for the initial stages of spindle pole body (SPB) duplication in yeast [1].
• Subsequently, we demonstrated extensive genetic interactions between the PKC1 pathway and the SPB duplication mutants that affect Cdc31p function [13].
• CDC31 is required for SPB duplication and encodes a calmodulin-like protein that is most closely related to caltractin/centrin, a protein associated with the Chlamydomonas basal body [6].
• We conclude that Kic1p function is dependent upon Cdc31p both in vivo and in vitro [7].

Analytical, diagnostic and therapeutic context of CDC31

• Molecular cloning of cDNA for caltractin, a basal body-associated Ca2+-binding protein: homology in its protein sequence with calmodulin and the yeast CDC31 gene product [14].
• Second, immunofluorescence staining indicates that CDC31 colocalizes with a known SPB component [15].
• Third, immunoelectron microscopy with whole cells and with isolated SPBs reveals that CDC31 is localized to the half bridge of the SPB, which lies immediately adjacent to the SPB plaques [15].
• Sequence analysis demonstrates that human centrin and centrins from higher plants, protozoa, algae, Xenopus and the yeast CDC31 gene product are closely related members of a subfamily of the EF-hand superfamily of calcium-binding proteins [16].

References