The critical role that the family of regulatory proteins known as cyclins plays in eukaryotic cell cycle regulation is well established. The best characterized cyclin complex is the mitotic cyclin B/Cdc2 p34 kinase, the active component of MPF (maturation promoting factor). Cyclin A accumulates prior to cyclin B in the cell cycle, appears to be involved in control of S phase and has been shown to associate with cyclin dependent kinase 2 (Cdk2). In addition, cyclin A has been implicated in cell transformation and is found in complexes with E1A, transcription factors DP-1 and E2F, and retinoblastoma protein p110. Two cyclin A-Cdk2 complex binding proteins, Skp1 p19 and Skp2 p45, have been described. Although the Skps (S phase kinase-associated proteins) associate with the active cyclin A-Cdk2 complex, they do not exhibit any regulatory effects on the complex. Abolition of Skp2 p45 function by either microinjection of anti-p45 antibodies or addition of antisense oligonucleotides prevents entry into S phase of both normal and transformed cells.