Open Access Publications
Permanent URI for this collection
Open access publications by faculty, staff, postdocs, and graduate students at the Center for Bioinformatics and Computational Biology.
Browse
Browsing Open Access Publications by Author "Ali, Asif"
Now showing 1 - 1 of 1
Results Per Page
Sort Options
Item Transcriptional regulation of Sis1 promotes fitness but not feedback in the heat shock response(eLife, 2023-05-17) Grade, Rania; Singh, Abhyudai; Ali, Asif; Pincus, DavidThe 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.