Identification of XDRP1;: a Xenopus protein related to yeast Dsk2p binds to the N-terminus of cyclin A and inhibits its degradation

Using the N-terminus of cyclin Al in a two-hybrid screen as a bait, we identified a Xenopus protein, XDRP1, that contains a ubiquitin-like domain in its N-terminus and shows significant homology in its C-terminal 50 residues to Saccharomyces cerevisiae Dsk2 and Schizosaccharomyces pombe dph1. XDRP1 is a nuclear phosphoprotein in Xenopus cells, and its phosphorylation is mediated by cyclin A-dependent kinase, XDRP1 binds to both embryonic and somatic forms of cyclin A (Al and A2) in Xenopus cells, but not to B-type cyclins. The N-terminal ubiquitin-like domain of XDRP1, but not the C-terminal Dsk2-like domain, is required for interaction with cyclin A. XDRP1 requires residues 130-160 of cyclin Al for efficient binding, which do not include the destruction box of cyclin A. The addition of bacterially expressed XDRP1 protein to frog egg extract inhibited the Ca2+-induced degradation of cyclin A, but not that of cyclin B, The injection of XDRP1 protein into fertilized Xenopus eggs blocked embryonic cell division.