Heat shock protein 70 binding inhibits the nuclear import of apoptosis-inducing factor

摘要: Heat shock protein 70 (HSP70) can inhibit apoptosis by neutralizing and interacting with apoptosis-inducing factor (AIF), a mitochondrial flavoprotein that translocates upon induction to the nucleus, via cytosol. Here, we show only members of HSP70 family interact AIF. Systematic deletion mapping revealed existence three distinct functional regions in AIF protein: (1) region between amino acids 150 228 binds HSP70, (2) domain residues 367 459 includes nuclear localization sequence (NLS) (3) C-terminal beyond residue 567 required for its chromatin-condensing activity. Deletion 150-268 completely abolished binding facilitated import AIF, resulting gain-of-function phenotype enhanced AIF-mediated chromatin condensation as compared wild-type This was observed control cells (which express low but significant levels HSP70), yet lost when AIFDelta150-268 introduced into knockout cells, underscoring importance AIF-HSP70 interaction. Altogether, our data demonstrate inhibition involves cytosolic retention Moreover, it appears endogenous are sufficiently elevated modulate lethal action