Heartfelt crosstalk: desensitization of the GIRK current

caspase-3 (ref. 18). It has been shown that overexpression of Hsp70 does not preclude the activation of a caspase-3-like activity, but prevents the downstream morphological changes that are characteristic of dying cells. With regard to Hsp27, Pandey et al. have recently reported direct binding and inhibition of caspase-3 processing by this protein. However, the authors failed to detect an effect of Hsp27 on release of cytochrome c, or on activation of Apaf-1 or caspase-9. In light of the findings of Bruey et al., Beere et al. and Saleh et al., as well as other observations showing an effect upstream of caspase activation, it remains to be determined whether these observations reflect a difference in signalling between different cell types or whether the results can be reconciled on the basis of some other experimental variable. In conclusion, the studies described both in Nature Cell Biology and elsewhere reveal an important connection between HSPs and the apoptotic machinery. Given that cellular homeostasis represents an equilibrium between survival and death, it follows that HSPs, as well as other chaperones, should play a pivotal role in maintaining this delicate balance.