Disease relevance of CDC23

• CDC23 or cdc23-39 genes cloned into a mobilizable YCp vector were then transferred directly from E. coli cultures to each suppressed yeast strain on the surfaces of agar plates [1].

High impact information on CDC23

• CDC23 is required at the metaphase/anaphase transition to separate sister chromatids, and we speculate that it might promote proteolysis of proteins that hold sister chromatids together [2].
• A repeating amino acid motif in CDC23 defines a family of proteins and a new relationship among genes required for mitosis and RNA synthesis [3].
• We have identified and characterized a novel, repeating 34 amino acid motif (the TPR motif) that is reiterated several times within the CDC23 gene product of S. cerevisiae [3].
• Entry into anaphase and proteolysis of B-type cyclins depend on a complex containing the tetratricopeptide repeat proteins Cdc16p, Cdc23p, and Cdc27p [4].
• Finally, we find that Rsi1p/Apc2p co-immunoprecipitates with Cdc23p [5].

Biological context of CDC23

• Most of these mutants lie in the CDC16, CDC23, and CDC27 genes, which have already been shown to play a role in cyclin proteolysis and encode components of a 20S complex (called the cyclosome or anaphase promoting complex) that ubiquitinates mitotic cyclins [6].
• The regulation of Cdc20 proteolysis reveals a role for APC components Cdc23 and Cdc27 during S phase and early mitosis [7].
• CDC23 is required in Saccharomyces cerevisiae for cell cycle progression through the G2/M transition [8].
• In this report we have used mutagenesis to probe the functional significance of the TPR units within CDC23 [8].
• The CDC23 gene product contains tandem, imperfect repeats, termed tetratricopeptide repeats, (TPR) units common to a protein family that includes several other nuclear division CDC genes [8].

Anatomical context of CDC23

• On the basis of these data, we conclude that Cdc23p localization was dependent on microtubules and was affected by specific types of kinetochore disruption [9].

Physical interactions of CDC23

• Furthermore, using recombinant molecules in vitro, we show that the N terminal of SIN1 is sufficient to bind a portion of CDC23 consisting solely of tetratrico peptide repeats [10].
• Swm1 also interacted with Cdc23 and Apc5 in this system [11].

Regulatory relationships of CDC23

• Mutations in the D box sequences of Clb2 inhibited interaction with Cdc23 both in vivo and in vitro [12].

Other interactions of CDC23

• The instability of Cdc20 depends on CDC23 and CDC27, which encode components of the APC [7].
• The Cdc16, Cdc23, and Cdc27 proteins all contain several copies of the tetratricopeptide repeat and are subunits of a complex that is required for the onset of anaphase [13].
• Hsl1p is stabilized by mutations in CDH1 and CDC23, both of which result in compromised APC activity [14].
• Association of yeast SIN1 with the tetratrico peptide repeats of CDC23 [10].
• Schizosaccharomyces pombe Cdc23 is an essential DNA replication protein, conserved in eukaryotes and functionally homologous with Saccharomyces cerevisiae Dna43 (Mcm10) [15].

Analytical, diagnostic and therapeutic context of CDC23

• Using two independent assays, two-hybrid analysis in vivo and co-immunoprecipitation in vitro, we demonstrate that Cdc16p, Cdc23p and Cdc27p self associate and interact with one another to form a macromolecular complex [16].

References