| First Author | Sjögren B | Year | 2015 |
| Journal | PLoS One | Volume | 10 |
| Issue | 5 | Pages | e0123581 |
| PubMed ID | 25970626 | Mgi Jnum | J:235324 |
| Mgi Id | MGI:5796081 | Doi | 10.1371/journal.pone.0123581 |
| Citation | Sjogren B, et al. (2015) FBXO44-Mediated Degradation of RGS2 Protein Uniquely Depends on a Cullin 4B/DDB1 Complex. PLoS One 10(5):e0123581 |
| abstractText | The ubiquitin-proteasome system for protein degradation plays a major role in regulating cell function and many signaling proteins are tightly controlled by this mechanism. Among these, Regulator of G Protein Signaling 2 (RGS2) is a target for rapid proteasomal degradation, however, the specific enzymes involved are not known. Using a genomic siRNA screening approach, we identified a novel E3 ligase complex containing cullin 4B (CUL4B), DNA damage binding protein 1 (DDB1) and F-box protein 44 (FBXO44) that mediates RGS2 protein degradation. While the more typical F-box partners CUL1 and Skp1 can bind FBXO44, that E3 ligase complex does not bind RGS2 and is not involved in RGS2 degradation. These observations define an unexpected DDB1/CUL4B-containing FBXO44 E3 ligase complex. Pharmacological targeting of this mechanism provides a novel therapeutic approach to hypertension, anxiety, and other diseases associated with RGS2 dysregulation. |
