@article{TEXTUAL,
      recid = {9832},
      author = {Garde, Rania and Singh, Abhyudai and Ali, Asif and Pincus,  David},
      title = {Transcriptional regulation of Sis1 promotes fitness but  not feedback in the heat shock response},
      journal = {eLife},
      address = {2023-05-09},
      number = {TEXTUAL},
      abstract = {The heat shock response (HSR) controls expression of  molecular chaperones to maintain protein homeostasis.  Previously, we proposed a feedback loop model of the HSR in  which heat-denatured proteins sequester the chaperone Hsp70  to activate the HSR, and subsequent induction of Hsp70  deactivates the HSR (Krakowiak et al., 2018; Zheng et al.,  2016). However, recent work has implicated newly  synthesized proteins (NSPs) – rather than unfolded mature  proteins – and the Hsp70 co-chaperone Sis1 in HSR  regulation, yet their contributions to HSR dynamics have  not been determined. Here, we generate a new mathematical  model that incorporates NSPs and Sis1 into the HSR  activation mechanism, and we perform genetic decoupling and  pulse-labeling experiments to demonstrate that Sis1  induction is dispensable for HSR deactivation. Rather than  providing negative feedback to the HSR, transcriptional  regulation of Sis1 by Hsf1 promotes fitness by coordinating  stress granules and carbon metabolism. These results  support an overall model in which NSPs signal the HSR by  sequestering Sis1 and Hsp70, while induction of Hsp70 – but  not Sis1 – attenuates the response.},
      url = {http://knowledge.uchicago.edu/record/9832},
}