Pharmacological targeting of endoplasmic reticulum stress in …
2021年10月26日 · This work provides the first evidence that prolongation of the ISR by inactivation of the inducible eIF2α phosphatase PPP1R15A renders mice resistant to ER stress-induced cell death.
PPP1R15A mRNA levels gradually re-turn to their initial level over a period of approximately 20 h, which delineates a window of cell adaptation to stress. Together, these results suggested that PPP1R15A mRNA contributes to the mo-lecular memory of the ISR, facilitating subsequent bursts of GADD34 synthesis and, hence, rapid changes in eIF2 phos-
Sensitization of the UPR by loss of PPP1R15A promotes fibrosis …
The unfolded protein response (UPR) is a direct consequence of cellular endoplasmic reticulum (ER) stress and a key disease driving mechanism in IPF. The resolution of the UPR is directed by PPP1R15A (GADD34) and leads to the restoration of normal ribosomal activity.
Preventing proteostasis diseases by selective inhibition of a ...
2015年4月10日 · SOD1 mutants bind to Derlin-1 on the cytosolic side of the ER membrane, blocking degradation of ER proteins and causing ER stress with pathological PPP1R15A signaling . Transgenic mice expressing the human ALS-causing mutant SOD1 G93A (SOD1 mutant mice) develop a motor neuron disease that closely resembles ALS ( 22 ).
Sensitization of the UPR by loss of PPP1R15A promotes fibrosis …
2021年11月3日 · PPP1R15A protein is undetectable by western blot in the fibroblast cell lysates (Fig. S2), and there is a clear increase upon stimulation with the ER stress inducer tunicamycin.
Protein phosphatase 1 regulatory subunit 15 A promotes …
2024年2月16日 · Protein Phosphatase 1 Regulatory Subunit 15 A (PPP1R15A), a stress-induced protein, promotes dephosphorylation of EIF2S1, TGF beta type I receptor and I-κ B kinase...
Collective cell migration relies on PPP1R15-mediated
2024年4月8日 · Our results support a model in which intrinsic physiological ER stress in normal border cells is actively restrained by dPPP1R15 to limit the PERK-p-eIF2α ER stress response (Figures 7 K and 7L). This allows the cluster to polarize, form stable front-directed protrusions, delaminate, and successfully migrate.
Protein phosphatase 1 subunit Ppp1r15a/GADD34 regulates cytokine ... - PNAS
2012年2月6日 · Here we show that in response to polyriboinosinic:polyribocytidylic acid (pI:C), DCs mount a specific integrated stress response during which the transcription factor ATF4 and the growth arrest and DNA damage-inducible protein 34 (GADD34/Ppp1r15a), a phosphatase 1 (PP1) cofactor, are expressed.
Salidroside attenuates sepsis-associated acute lung injury through ...
2022年10月1日 · The expressions of PPP1R15A and endoplasmic reticulum (ER) stress-related genes were detected by quantitative reverse transcription polymerase chain reaction and western blot. And the effects of silenced PPP1R15A and tauroursodeoxycholic acid (TUDCA) on cell viability, apoptosis and endoplasmic reticulum (ER) stress were determined by cell ...
Salidroside attenuates sepsis-associated acute lung injury through ...
2022年10月1日 · The expression of PPP1R15A was decreased in sepsis models and increased by salidroside, and salidroside down-regulated the ER stress-related protein expressions in vitro and in vivo. Silenced PPP1R15A reversed the effect of salidroside on cell viability, apoptosis and ER stress, whereas TUDCA could counteract the above effect of silenced PPP1R15A.