2023.04.04
REASERCH
Our new paper is out in Leukemia!
Our new paper, led by Fumihiko, is now available here! https://www.nature.com/articles/s41375-023-01879-z
Our findings reveal that a mitochondrial E3 ubiquitin ligase complex, consisting of MARCH5, UBE2J2, and/or UBE2K, regulates AML cell-intrinsic resistance to Venetoclax (VEN). This regulation occurs by modulating NOXA protein stability. The MARCH5 E3 ligase complex constantly ubiquitinates NOXA, leading to proteasome-mediated degradation, which in turn modulates BAX saturation of anti-apoptotic proteins. Our results suggest increased NOXA protein levels primarily account for enhanced VEN sensitivity in MARCH5-depleted AML cells.
Our findings reveal that a mitochondrial E3 ubiquitin ligase complex, consisting of MARCH5, UBE2J2, and/or UBE2K, regulates AML cell-intrinsic resistance to Venetoclax (VEN). This regulation occurs by modulating NOXA protein stability. The MARCH5 E3 ligase complex constantly ubiquitinates NOXA, leading to proteasome-mediated degradation, which in turn modulates BAX saturation of anti-apoptotic proteins. Our results suggest increased NOXA protein levels primarily account for enhanced VEN sensitivity in MARCH5-depleted AML cells.