CONICET | Buscador de Institutos y Recursos Humanos

F-box proteins and DCAF proteins are the substrate binding subunits of SCF (Skp1-Cul1-F-box protein) and CRL4 (Cul4-RING protein Ligase)ubiquitin ligase complexes, respectively. Using affinity purification and mass spectrometry, we determined that the F-box protein FBXO11 interacts with CDT2, a DCAF protein that controls cell cycle progression, and recruits CDT2 to the SCFFBXO11complex to promote its proteasomal degradation. In contrast to most SCF substrates, which exhibit phosphodegron-dependent binding to F-box proteins, CDK-mediated phosphorylation of Thr464 present in the CDT2 degron inhibits recognition by FBXO11. Finally, our results show that the functional interaction between FBXO11 and CDT2 is evolutionary conserved from worms to humans and plays an important role in regulating the timing of cell cycle exit.