The novel agent G9 can induce apoptosis in B-cell tumors through inhibition of 3 DUBs (Usp9x, Usp24, and Usp5). Usp9x and Usp24 are DUBs for Mcl-1; therefore, G9 treatment allows ubiquitinated Mcl-1 to be degraded by the proteasome. Usp5 targets unanchored polyubiquitin.10 Accumulation of this complex competes for proteasome binding with ubiquitinated p53; therefore, G9 treatment results in the accumulation of proapoptotic p53. Professional illustration by Ken Probst, XavierStudio.
