Inhibition of proteolytic and ATPase activities of the proteasome by the BTK inhibitor CGI-1746.

Bruton's tyrosine kinase (BTK) inhibitor, ibrutinib, has been shown to synergize with proteasome inhibitors (PIs) in reducing the viability of cells derived from B cell malignancies, but the mechanism is not known. We report here that an off-target effect of ibrutinib causes synergy because not all BTK inhibitors exhibited the synergistic effect, and those that synergized did so even in cells that do not express BTK. The allosteric BTK inhibitor CGI-1746 showed the strongest synergy.

Telomerase Does Not Improve DNA Repair in Mitochondria upon Stress but Increases MnSOD Protein under Serum-Free Conditions.

Telomerase is best known for its function in maintaining telomeres but has also multiple additional, non-canonical functions. One of these functions is the decrease of oxidative stress and DNA damage due to localisation of the telomerase protein TERT into mitochondria under oxidative stress. However, the exact molecular mechanisms behind these protective effects are still not well understood.