| First Author | Huang OW | Year | 2012 |
| Journal | Nat Struct Mol Biol | Volume | 19 |
| Issue | 2 | Pages | 171-5 |
| PubMed ID | 22245969 | Mgi Jnum | J:229517 |
| Mgi Id | MGI:5752246 | Doi | 10.1038/nsmb.2206 |
| Citation | Huang OW, et al. (2012) Phosphorylation-dependent activity of the deubiquitinase DUBA. Nat Struct Mol Biol 19(2):171-5 |
| abstractText | Addition and removal of ubiquitin or ubiquitin chains to and from proteins is a tightly regulated process that contributes to cellular signaling and protein stability. Here we show that phosphorylation of the human deubiquitinase DUBA (OTUD5) at a single residue, Ser177, is both necessary and sufficient to activate the enzyme. The crystal structure of the ubiquitin aldehyde adduct of active DUBA reveals a marked cooperation between phosphorylation and substrate binding. An intricate web of interactions involving the phosphate and the C-terminal tail of ubiquitin cause DUBA to fold around its substrate, revealing why phosphorylation is essential for deubiquitinase activity. Phosphoactivation of DUBA represents an unprecedented mode of protease regulation and a clear link between two major cellular signal transduction systems: phosphorylation and ubiquitin modification. |
