Identification of XDRP1; a Xenopus protein related to yeast Dsk2p binds tothe 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 iden tified a Xenopus protein, XDRP1, that contains a ubiquitin-like domain in i ts 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 me diated by cyclin A-dependent kinase, XDRP1 binds to both embryonic and soma tic forms of cyclin A (Al and A2) in Xenopus cells, but not to B-type cycli ns. The N-terminal ubiquitin-like domain of XDRP1, but not the C-terminal D sk2-like domain, is required for interaction with cyclin A. XDRP1 requires residues 130-160 of cyclin Al for efficient binding, which do not include t he destruction box of cyclin A. The addition of bacterially expressed XDRP1 protein to frog egg extract inhibited the Ca2+-induced degradation of cycl in A, but not that of cyclin B, The injection of XDRP1 protein into fertili zed Xenopus eggs blocked embryonic cell division.