Alternative titles; symbols
HGNC Approved Gene Symbol: CDC34
Cytogenetic location: 19p13.3 Genomic coordinates (GRCh38): 19:531,760-542,087 (from NCBI)
Normal eukaryotes from yeasts to humans have a conserved checkpoint mechanism in cell division for maintenance of genomic stability. After DNA strand breaks, checkpoint genes induce rest in the G1 and G2 phases of the cell cycle until the damage is repaired. Plon et al. (1993) isolated a putative human G2 checkpoint gene, a homolog of the CDC34 gene of Saccharomyces cerevisiae. Human CDC34 could substitute efficiently for yeast CDC34.
Using deletion and site-directed mutagenesis experiments, Semplici et al. (2002) demonstrated that CK2 (see 115440) phosphorylated CDC34 and UBC3B (UBE2R2; 612506) at a corresponding serine residue in the C terminus of each protein. In vitro binding experiments demonstrated that phosphorylated UBC3B and CDC34 bound specifically to the F-box protein beta-TRCP (BTRC; 603482), which resulted in enhanced degradation of beta-catenin (116806), a substrate of BTRC. Semplici et al. (2002) suggested that CK2-dependent phosphorylation of CDC34 and UBC3B functions by regulating BTRC substrate recognition.
Pierce et al. (2009) developed a quantitative framework based on product distribution that predicted that the really interesting new gene (RING) E3 enzymes SCF(Cdc4) (606278) and SCF-beta-TrCP (603482) work with the E2 Cdc34 to build polyubiquitin chains on substrates by sequential transfers of single ubiquitins. Measurements with millisecond time resolution directly demonstrated that substrate polyubiquitylation proceeds sequentially. Pierce et al. (2009) concluded that their results presented an unprecedented glimpse into the mechanism of RING ubiquitin ligases and illuminated the quantitative parameters that underlie the rate and pattern of ubiquitin chain assembly.
Plon et al. (1993) demonstrated by in situ hybridization that the CDC34 gene is located in the far telomeric region of 19p13.3, in a region of syntenic homology between human 19p and mouse 11.
Pierce, N. W., Kleiger, G., Shan, S., Deshaies, R. J. Detection of sequential polyubiquitylation on a millisecond timescale. Nature 462: 615-619, 2009. [PubMed: 19956254] [Full Text: https://doi.org/10.1038/nature08595]
Plon, S. E., Leppig, K. A., Do, H.-N., Groudine, M. Cloning of the human homolog of the CDC34 cell cycle gene by complementation in yeast. Proc. Nat. Acad. Sci. 90: 10484-10488, 1993. [PubMed: 8248134] [Full Text: https://doi.org/10.1073/pnas.90.22.10484]
Semplici, F., Meggio, F., Pinna, L. A., Oliviero, S. CK2-dependent phosphorylation of the E2 ubiquitin conjugating enzyme UBC3B induces its interaction with beta-TrCP and enhances beta-catenin degradation. Oncogene 21: 3978-3987, 2002. [PubMed: 12037680] [Full Text: https://doi.org/10.1038/sj.onc.1205574]