Figure 3.

Trbl upstream regulation and candidate downstream targets. (A) Based on work from Gerlach et al., a comprehensive pathway of Tribbles function incorporates Hippo regulation by the bantam miRNA [108]. (B) Alignment of the Trib degron from human C/EBP proteins and the Drosophila C/EBP ortholog, Slbo, with candidate proteins from the Drosophila genome. Methods: A protein-protein BLAST search was conducted of non-redundant Drosophila sequences derived from the GenBank coding sequence (CDS) translations (including the PDB [Protein Data Bank], SwissProt, PIR [Protein Information Resource], and PRF [Protein Research Foundation]) with four sequences derived from the degron Slbo (ICEhEtSIDISAYIDPAA). The four sequences (JXXXEXTJDJXXXID, JXXXEXSJDJXXXID, LXXXEXTLDLXXXID, and IXXXEXTIDIXXXID) were chosen to exclude poorly conserved residues (X) and include where possible ambiguous amino acids (B, Z, and J) with the goal of expanding the binding sites obtained from the search. More functional data to evaluate important residues in the candidate binding sites was absent and top-ranked homologies overall are listed followed by strong homologies to subdomains of the motif.