Biology 3355A/B Study Guide - Midterm Guide: Hsf1, Atf4, Hsp90

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Unfolded protein has hydrophobic domains which compete and have higher affinity for hsp90, which is the sensor of the hs pathway. Hse consensus sequences of the promoter region of target genes hsp27/hsp70, which can induce genes involved in cell survival including protein refolding, increasing gsh, modulating actin, Ptms can occur on hsf1 as well: acetylation, phosphorylation, and subsequently sumoylation. Hsp40 delivers unfolded protein to atp-hsp70 (open conformation; low affinity) via its hydrophobic peptide segments. Hsp40 induces atp hydrolysis, so adp-hsp70 is present to do conformational change to hold protein in place, and fold it properly. Unfolded proteins bind to bip (higher affinity) so bip disassociates from signaling molecule: perk is able to dimerize, and then autophosphorylate itself and eif2a to stop general protein synthesis. Atf4 ends up being expressed in delayed translation reinitiation upregulating genes involved in pro-survival (chaperones, xbp1, antioxidants).

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