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. 2020 Dec 8;11:6271. doi: 10.1038/s41467-020-20000-x

Fig. 7. Hypothetical model for Sis1 function in regulating the stress response.

Fig. 7

a Normal Sis1 levels. Htt97Q aggregates form dense inclusions that are inaccessible to Hsp70. HSF1 remains Hsp70-bound and inactive. HSE, heat shock element in the promoter. b Elevated Sis1 interacts with soluble polyQ oligomers and mediates their coalescence into cloud-like condensates that are permeable to Hsp70. As a result, Hsp70 is titrated away from HSF1, activating the HSR. Active HSF1 is shown as a trimer. c Normal Sis1 levels. During heat stress, Sis1 recruits Hsp70 to conformationally destabilized (misfolded) protein species. As a result, Hsp70 is titrated away from HSF1, activating the HSR. d Elevated Sis1 levels recruit an increased amount of Hsp70 to misfolded proteins during stress, resulting in a hyperactive, maladapted stress response.