Disease relevance of CDC27

• The human homolog of the Saccharomyces cerevisiae cell division control 27 gene (CDC27) was mapped to human chromosome 17q12-q21 using a panel of human/rodent somatic cell hybrids and localized distal to the breast cancer susceptibility gene, BRCA1, using a panel of radiation hybrids [1].
• The adenovirus YAC could be manipulated efficiently using homologous recombination-based methods in the yeast host, and mutant viruses, including a variant that expresses the human analog of the Saccharomyces cerevisiae CDC27 gene, were readily recovered from modified derivatives of the YAC [2].

High impact information on CDC27

• We conclude that CDC27 and CDC16 are evolutionarily conserved components of the centrosome and mitotic spindle that control the onset of postmetaphase events during mitosis [3].
• Injection of affinity-purified anti-CDC27Hs antibodies into logarithmically growing HeLa cells causes a highly reproducible cell cycle arrest in metaphase with apparently normal spindle structure [3].
• CDC27Hs colocalizes with CDC16Hs to the centrosome and mitotic spindle and is essential for the metaphase to anaphase transition [3].
• This led to the identification of a mutated form of human CDC27, which gave rise to an HLA-DR4-restricted melanoma antigen [4].
• The Arabidopsis HOBBIT gene encodes a CDC27 homolog that links the plant cell cycle to progression of cell differentiation [5].

Biological context of CDC27

• Localization of the human homolog of the yeast cell division control 27 gene (CDC27) proximal to ITGB3 on human chromosome 17q21.3 [1].
• Further confirmation of this localization comes from the sequence tagged site (STS) mapping of human CDC27 to the same yeast artificial chromosomes (YACs) positive for ITGB3 [1].
• Linking yeast genetics to mammalian genomes: identification and mapping of the human homolog of CDC27 via the expressed sequence tag (EST) data base [6].
• The sequence homology and organization of the 10 repeats are similar to those of the nuc2 protein of fission yeast and bimA protein of Aspergillus, which suggests that the newly identified protein could be the human homologue of nuc2 (H-NUC) [7].
• Kinases that also associate with isolated chromosomes catalyzed the in vitro phosphorylation of the chromosome-associated Cdc27 [8].

Anatomical context of CDC27

• We examined the subcellular distribution of Cdc27 in greater detail in mammalian cells and found Cdc27 concentrated at spindle poles and on spindle microtubules as previously described, but also found Cdc27 at kinetochores and along chromosome arms [8].

Associations of CDC27 with chemical compounds

• The radiation hybrid panel indicates that the most likely position of human CDC27 on human chromosomes 17 is between the marker D17S409 and the beta 3 subunit of integrin (ITGB3) [1].
• The serine/threonine phosphatase PP5 interacts with CDC16 and CDC27, two tetratricopeptide repeat-containing subunits of the anaphase-promoting complex [9].

Physical interactions of CDC27

• We further provide biochemical evidence that the C-terminus of APC10 binds to CDC27/APC3, an APC subunit that contains multiple tetratrico peptide repeats [10].

Regulatory relationships of CDC27

• Therefore, APC 3 x 15 domain plays a positive role in the control of transcriptional activity of beta-catenin-TCF-4 and can contribute to explain the role of the truncated forms of APC in colon tumorigenesis [11].

Other interactions of CDC27

• The estimated distance between ITGB3 and human CDC27 is less than 600 kb [1].
• In the present report, we demonstrate that the inhibitory association between Mad2 and the APC component Cdc27 also takes place transiently during the early stages of a normal mitosis and is lost before mitotic exit [12].
• Consistent with the notion that Tax activates APC(Cdc20) directly, Tax is found to coimmunoprecipitate with Cdc20 and Cdc27/APC3 [13].
• Here we show by a combination of two-hybrid analysis and in vitro binding that PP5 interacts with CDC16 and CDC27, two subunits of the anaphase-promoting complex [9].
• Moreover, previous binding of APC 3 x 15 facilitates the association of beta-catenin to the TATA box-associated protein [11].

Analytical, diagnostic and therapeutic context of CDC27

• Microinjection of anti-Cdc27 antibody into cells causes arrest at metaphase [8].
• Comparative protein sequence analysis identifies a protein sequence motif, called the DNA polymerase interaction motif (DPIM), in Cdc27 orthologues from a wide variety of eukaryotic species, including mammals [14].

References