The Quest for Substrates for SCF -Trcp2 Ubiquitin Ligase: Crosstalk between Phosphorylation and Ubiquitination

SCF ligases are a class of E3 enzymes composed of Skp1, Cullin 1, a RING-_nger protein (Rbx1 or Rbx2) and a variable component known as the F-box protein. The F-box protein family recognizes and captures specific substrates that are subsequently ubiquitinated by E2 ubiquitin-conjugating enzymes. For a number of the well-studied F-box substrates, such as Fbw7, Skp2 and _-Trcp, substrate binding requires the presence of unique phosphorylated motifs (phosphodegrons) on the substrates, indicating crosstalk between phosphorylation and ubiquitination.

For instance, β-Trcp is an F-box protein containing WD repeats that bind speci_c substrates haboring the DSpGXX(X)Sp motif.