HumanCDC23:cDNA Cloning, Mapping to 5q31, Genomic Structure, and Evaluation as a Candidate Tumor Suppressor Gene in Myeloid Leukemias

Abstract

The transition from metaphase to anaphase and exit from mitosis involve the degradation of active cyclin B–CDC2 complexes by ubiquitin-mediated proteolysis. The anaphase-promoting complex (APC) catalyzes the formation of cyclin B–ubiquitin conjugates, thereby targeting cyclin B for degradation. The APC is composed of eight proteins, including four members of a family characterized by multiple tetratricopeptide repeats (TPR). We mapped two overlapping expressed sequence tag clones within a genomic contig on human chromosome 5, band q31. A search revealed high homology toSaccharomyces cerevisiaeCDC23, a TPR protein component of the APC. We have isolated the humanCDC23cDNA containing the full-length predicted open reading frame. The ∼3.3-kb message is ubiquitously expressed and encodes a protein with 591 amino acids (MW = 68,293 Da) and 9 TPR units. The protein has 30% identity and 51% similarity to theS. cerevisiaeprotein. The humanCDC23gene contains 16 exons and spans ∼31 kb.CDC23maps within the smallest commonly deleted segment in myeloid leukemias characterized by a deletion of 5q; however, we detected no mutations ofCDC23in leukemia cells with loss of 5q. Thus,CDC23is unlikely to be involved in the pathogenesis of myeloid leukemias characterized by abnormalities of chromosome 5.