Environmental, physiological, and pathological stimuli induce the misfolding of proteins, which results in the formation of aggregates and amyloid fibrils. To cope with proteotoxic stress, cells are equipped with adaptive mechanisms that are accompanied by changes in gene expression. The evolutionarily conserved mechanism called the heat shock response is characterized by the induction of a set of heat shock proteins (HSPs), and is mainly regulated by heat shock transcription factor 1 (HSF1) in mammals. We herein introduce the mechanisms by (...) which HSF1 tightly controls the transcription of HSP genes via the regulation of pre‐initiation complex recruitment in their promoters under proteotoxic stress. These mechanisms involve the stress‐induced regulation of HSF1‐transcription complex formation with a number of coactivators, changes in chromatin states, and the formation of phase‐separated condensates through post‐translational modifications. (shrink)

Beyond protein synthesis and autophagy, emerging evidence has implicated mTORC1 in regulating protein folding and proteasomal degradation as well, highlighting its prominent role in cellular proteome homeostasis or proteostasis. In addition to growth signals, mTORC1 senses and responds to a wide array of stresses, including energetic/metabolic stress, genotoxic stress, oxidative stress, osmotic stress, ER stress, proteotoxic stress, and psychological stress. Whereas growth signals unanimously stimulate mTORC1, stresses exert complex impacts on mTORC1, most of which are repressive. mTORC1 suppression, as a (...) generic adaptive strategy, empowers cell survival under various stressful conditions. In this essay, we provide an overview of the emerging role of mTORC1 in proteostasis, the distinct molecular mechanisms through which mTORC1 reacts to diverse stresses, and the schemes exploited by cancer cells to circumvent stress‐induced mTORC1 suppression. Hence, acting as a stress sensor, mTORC1 intimately couples stresses to cellular proteostasis. (shrink)

It is useful to envision two fundamentally different ways by which the timing of plant development is regulated: developmental stage‐transition mechanisms and time‐to‐flowering mechanisms. The existence of both mechanisms is indicated by the behavior of various mutants. Shoot stage transitions are defined by dominant mutants representing at least four different genes; each mutant retards transitions from juvenile shoot stages to more adult shoot stages. In addition, dominant leaf stage‐transition mutants in at least seven different genes have similar phenotypes, but the (...) leaf rather than the shoot is the. focus (and at least two of these genes encode domain proteins.) One mutant, Hairy sheath frayed 1‐0 (Hsf1‐O) simultaneously affects shoot and leaf; this mutant's behavior initiated our interest in plant heterochronism(1). The second type of timekeeping involves time‐to‐flowering. As with most plant but not animals species, cultivars of the maize species vary greatly for the time‐to‐flowering quantitative trait: between 6 and 14 weeks is common. It is via the 'slipping time frames' interaction that takes place between stage‐transition mutants and time‐to‐flowering genetic back‐grounds that unexpected and radical phenotypes occur. We see a reservoir of previously unsuspected morphological possibilities among the few heterochronic genotypes we have constructed, possibilities that may mimic the sort of variation needed to fuel macroevolution without having to posit (as done by Goldschmidt(2)) any special macromutational mechanisms. (shrink)