| First Author | Yao Q | Year | 2018 |
| Journal | Biochem Biophys Res Commun | Volume | 503 |
| Issue | 4 | Pages | 3192-3197 |
| PubMed ID | 30146258 | Mgi Jnum | J:272942 |
| Mgi Id | MGI:6280807 | Doi | 10.1016/j.bbrc.2018.08.123 |
| Citation | Yao Q, et al. (2018) The C-terminus of Ubl4A is critical for pro-death activity and association with the Arp2/3 complex. Biochem Biophys Res Commun 503(4):3192-3197 |
| abstractText | Ubl4A is a small ubiquitin-like protein involved in diverse cellular functions. We have shown that Ubl4A is critical for survival of the starvation-mediated cell death in vivo. The underlying mechanism for this is through interaction with the actin-related protein Arp2/3 complex and promotion of actin branching. Interestingly, "put-back" of Ubl4A to Ubl4A-deficient cells also results in cell death. Removal of the Ubl4A N-terminus significantly enhances its cytotoxicity, indicating that the pro-death activity of Ubl4A is mainly from its C-terminal region. In vitro protein pull-down assays show that the C-terminal region of Ubl4A can directly interact with the Arp2/3 complex. The single point mutation of an aspartic acid to alanine (D122A) in the Ubl4A C-terminus abolishes its ability to bind the Arp2/3 complex. This mutation also destabilizes Ubl4A proteins susceptible to protease degradation. Importantly, ectopic expression of wild-type Ubl4A can induce cell death in colon cancer cells, but such pro-death activity is diminished in the D122A mutant. These data suggest that Ubl4A C-terminus, especially D122, is critical for Ubl4A-Arp2/3 interaction and its pro-death function. |
