Authors: Vinay Dahiya, Ganesh Agam, Jannis Lawatscheck, Daniel Andreas Rutz, Don C. Lamb, Johannes Buchner
Summary: p53, the guardian of the genome, requires chaperoning by Hsp70 and Hsp90. However,how the two chaperone machineries affect p53 conformation and regulate its functionremains elusive. We found that Hsp70, together with Hsp40, unfolds p53 in an ATP-dependentreaction. This unfolded state of p53 is susceptible to aggregation after release inducedby the nucleotide exchange factor Bag-1. However, when Hsp90 and the adaptor proteinHop are present, p53 is transferred from Hsp70 to Hsp90, allowing restoration of thenative state upon ATP hydrolysis. Our results suggest that the p53 conformation isconstantly remodeled by the two major chaperone machineries. This connects p53 activityto stress, and the levels of free molecular chaperones are important factors regulatingp53 activity. Together, our findings reveal an intricate interplay and cooperationof Hsp70 and Hsp90 in regulating the conformation of a client.
Source: Molecular Cell, 2019; 74 (4): 816