| First Author | Li XY | Year | 2014 |
| Journal | Mol Cell | Volume | 53 |
| Issue | 3 | Pages | 407-19 |
| PubMed ID | 24412064 | Mgi Jnum | J:210542 |
| Mgi Id | MGI:5571424 | Doi | 10.1016/j.molcel.2013.12.008 |
| Citation | Li XY, et al. (2014) RIG-I modulates Src-mediated AKT activation to restrain leukemic stemness. Mol Cell 53(3):407-19 |
| abstractText | Retinoic acid (RA)-inducible gene I (RIG-I) is highly upregulated and functionally implicated in the RA-induced maturation of acute myeloid leukemia (AML) blasts. However, the underlying mechanism and the biological relevance of RIG-I expression to the maintenance of leukemogenic potential are poorly understood. Here, we show that RIG-I, without priming by foreign RNA, inhibits the Src-facilitated activation of AKT-mTOR in AML cells. Moreover, in a group of primary human AML blasts, RIG-I reduction renders the Src family kinases hyperactive in promoting AKT activation. Mechanistically, a PxxP motif in RIG-I, upon the N-terminal CARDs' association with the Src SH1 domain, competes with the AKT PxxP motif for recognizing the Src SH3 domain. In accordance, mutating PxxP motif prevents Rig-I from inhibiting AKT activation, cytokine-stimulated myeloid progenitor proliferation, and in vivo repopulating capacity of leukemia cells. Collectively, our data suggest an antileukemia activity of RIG-I via competitively inhibiting Src/AKT association. |
