|Chipping away at HSP70 regulation
This week’s Nature presents an elegant article by Cam Patterson’s group documenting a novel regulatory axis controlling Hsp70 levels. CHIP is a ubiquitin ligase that binds to Hsp70. CHIP is known to mediate induction of Hsp70 in response to stress by inducing activity of the transcription factor HSF-1. The current manuscript describes a second point in the regulatory axis of Hsp70 where CHIP acts. Patterson’s group found that CHIP mediates degradation of Hsp70 during the recovery phase after stress has been quenched. An elegant aspect of this model is that CHIP senses the level of misfolded proteins, and as the level of misfolded proteins decreases, CHIP switches from ubiquitinating these proteins to ubiquitinating Hsp70, which targets it for degradation by the proteasome. Thus, CHIP acts at two points in the regulation of Hsp70. CHIP regulates the transcription of Hsp70 (via HSF-1) and regulates degradation of Hsp70 (via ubiquitination of Hsp70).
The disposition of misfolded proteins is clearly one of the central issues in...