Stayin' alive: BCL-2 proteins in the hematopoietic system.

BH3 mimetics constitute a novel concept of antitumor therapy, inducing apoptosis via inhibition of pro-survival BCL-2 proteins. Programmed cell death is fundamental for physiological hematopoiesis; hence hematological side effects of these compounds are conceivable. Navitoclax and venetoclax have been studied extensively in the clinical setting; our knowledge of the more recently developed BCL-2 protein inhibitors specifically targeting MCL-1 or BCL-X, however, is restricted mainly to preclinical experiments.

Global kinome profiling reveals DYRK1A as critical activator of the human mitochondrial import machinery.

The translocase of the outer mitochondrial membrane TOM constitutes the organellar entry gate for nearly all precursor proteins synthesized on cytosolic ribosomes. Thus, TOM presents the ideal target to adjust the mitochondrial proteome upon changing cellular demands. Here, we identify that the import receptor TOM70 is targeted by the kinase DYRK1A and that this modification plays a critical role in the activation of the carrier import pathway.