Project description:The Heat Shock response (HSR) is a highly conserved transcriptional program induced by the exposure to a variety of environmental stressors. Following an insult, a small subset of genes, known as the Heat Shock genes, are rapidly induced by the Heat Shock Factors (HSFs) to maintain protein homeostasis and ensure cell survival. In this study, we demonstrate that the RNAPII interactor RPRD1B is required for proper transcription of heat shock induced genes and for survival to heat shock.
Project description:The Heat Shock response (HSR) is a highly conserved transcriptional program induced by the exposure to a variety of environmental stressors. Following an insult, a small subset of genes, known as the Heat Shock genes, are rapidly induced by the Heat Shock Factors (HSFs) to maintain protein homeostasis and ensure cell survival. In this study, we demonstrate that the RNAPII interactor RPRD1B is required for proper transcription of heat shock induced genes and for survival to heat shock.
Project description:Whole-genome analysis of heat shock factor binding sites in Drosophila melanogaster. Heat shock factor IP DNA or Mock IP DNA from heat shocked Kc 167 cells compared to whole cell extract on Agilent 2x244k tiling arrays.
Project description:Cells respond to stress by synthesising chaperone proteins that correct protein misfolding to maintain function. However, protein homeostasis is lost in ageing, leading to aggregates characteristic of protein-folding diseases. Whilst much is known about how these diseases progress, discovering what causes protein-folding to deteriorate could be key to their prevention. Here, we examined primary human mesenchymal stem cells (hMSCs), cultured to a point of replicative senescence and subjected to heat shock, as an in vitro model of the ageing stress response. We found through proteomic analysis that the maintenance of homeostasis deteriorated in senescent cells, coincident with lowered levels of a functional module of chaperone proteins associated with heat shock protein 70 kDa (HSPA1A). Further analysis of the temporal dynamics of the proteomic and transcriptomic stress response revealed a lack of translational capacity to be a limiting factor in the capacity of senescent cells to mitigate proteotoxic stress.
Project description:Heat shock response (HSR) is a cellular defense mechanism against various stresses. Both heat shock and proteasome inhibitor MG132 cause the induction of heat shock proteins, a distinct feature of HSR. To better understand the molecular basis of HSR, we subjected the mouse fibrosarcoma cell line, RIF-1, and its thermotolerant variant, TR-RIF-1 cells, to heat shock and MG132. We compared mRNA expressions using microarray analysis during recovery after heat shock and MG132 treatment. This study led us to group the 3,245 up-regulated genes by heat shock and MG132 into three families: genes regulated 1) by both heat shock and MG132 (e.g. chaperones); 2) by heat shock (e.g. DNA-binding proteins including histones); and 3) by MG132 (e.g. innate immunity and defense-related molecules).
Project description:Cells respond to stress by synthesising chaperone proteins that correct protein misfolding to maintain function. However, protein homeostasis is lost in ageing, leading to aggregates characteristic of protein-folding diseases. Whilst much is known about how these diseases progress, discovering what causes protein-folding to deteriorate could be key to their prevention. Here, we examined primary human mesenchymal stem cells (hMSCs), cultured to a point of replicative senescence and subjected to heat shock, as an in vitro model of the ageing stress response. We found through proteomic analysis that the maintenance of homeostasis deteriorated in senescent cells, coincident with lowered levels of a functional module of chaperone proteins associated with heat shock protein 70 kDa (HSPA1A). Further analysis of the temporal dynamics of the proteomic and transcriptomic stress response revealed a lack of translational capacity to be a limiting factor in the capacity of senescent cells to mitigate proteotoxic stress.
