| First Author | Li K | Year | 2017 |
| Journal | Cancer Cell | Volume | 31 |
| Issue | 5 | Pages | 697-710.e7 |
| PubMed ID | 28486108 | Mgi Jnum | J:242575 |
| Mgi Id | MGI:5905685 | Doi | 10.1016/j.ccell.2017.04.006 |
| Citation | Li K, et al. (2017) TRIB3 Promotes APL Progression through Stabilization of the Oncoprotein PML-RARalpha and Inhibition of p53-Mediated Senescence. Cancer Cell 31(5):697-710.e7 |
| abstractText | Acute promyelocytic leukemia (APL) is driven by the oncoprotein PML-RARalpha, which antagonizes myeloid differentiation and promotes APL-initiating cell self-renewal. Combined all-trans retinoic acid (ATRA) with arsenic trioxide (As2O3) or chemotherapy dramatically improves the prognosis of APL patients. Here we report that expression of pseudokinase Tribble 3 (TRIB3) associates positively with APL progression and therapeutic resistance. The elevated TRIB3 expression promotes APL by interacting with PML-RARalpha and suppressing its sumoylation, ubiquitylation, and degradation. This represses PML nuclear body assembly, p53-mediated senescence, and cell differentiation, and supports cellular self-renewal. Genetically inhibiting TRIB3 expression or combination of a peptide disturbing TRIB3/PML-RARalpha interaction with ATRA/As2O3 eradicates APL by accelerating PML-RARalpha degradation. Our study provides insight into APL pathogenesis and a potential therapeutic option against APL. |
