2023年9月8日 · Reconstitution of ISR activation with recombinant proteins demonstrates that PERK and PKR inhibitors directly activate dimeric GCN2, following a Gaussian activation-inhibition curve, with...

eif2α磷酸化由四种激酶介导，即gcn2、perk、pkr和 hri 每个磷酸化的eif2α对不同的应激源有反应。氨基酸的减少刺激了绿色通道2；perk对一种叫做内质网的组织中未折叠蛋白质的存在作出反应；在病毒感染期间，当双链核糖核酸在细胞质中积累时，pkr起作用；并且当 ...

Our results demonstrate that PERK and GCN2 function to cooperatively regulate eIF2α phosphorylation and cyclin D1 translation after UPR activation. Integral membrane proteins and secreted proteins are synthesized, folded, and posttranslationally modified in …

2016年9月16日 · Four eIF2α kinases, namely heme-regulated inhibitor (HRI), protein kinase R (PKR), PKR-like endoplasmic reticulum kinase, (PERK) and general control non-depressible 2 (GCN2), have been...

2020年9月15日 · To test the conjecture that GCN2 compensates for PERK inactivation and to explore further the mechanism for PERK regulation, we investigated the effects of the chemotherapeutic drugs on PERK and GCN2 signalling in the drug sensitive and resistant MCF-7 breast cancer cells.

整合应激反应 （integrated stress response ISR）是蛋白质稳态失调时诱发的信号中心调控网络，主要以控制蛋白质合成速率来实现。 2020年4月24日，美国贝勒医学院的 Mauro Costa-Mattioli 和UCSF大学的 Peter Walter 在 Science 上发表题为 The integrated stress response: From mechanism to disease 综述。 本综述总结了ISR调控机制以及ISR异常时如何导致复杂疾病发生，包括认知障碍、神经退行性疾病、肿瘤和糖尿病等。 最后作者指出开发出调控ISR的有效药 …

2020年9月9日 · To explore the potential mechanisms involved, we performed time-course drug treatment experiments on the parental MCF-7 and drug resistant MCF-7Epi R and MCF-7Tax R breast cancer cells and identified GCN2 (eIF2AK4) as a molecule that can potentially cooperate with PERK to regulate FOXO3 via JNK and AKT to modulate drug response.

Exposure of cells to endoplasmic reticulum (ER) stress leads to activation of PKR-like ER kinase (PERK), eukaryotic translation initiation factor 2alpha (eIF2alpha) phosphorylation, repression of cyclin D1 translation, and subsequent cell cycle arrest in G1 phase. However, whether PERK is …

2018年7月24日 · PERK and GCN2 are eIF2α kinases known to mediate the effects of ER stress and respond to an array of diverse stress stimuli. Previously, we reported that ER stress potentiates insulin resistance through PERK-mediated FOXO phosphorylation. Inhibition of PERK improves cellular insulin responsiveness at the level of FOXO activity.

2023年6月9日 · PERK and GCN2 share considerable functional redundancy in the integrated stress response and their functions can overlap (Hamanaka et al, 2005; Lehman et al, 2015). To investigate whether PERK shares the mitotic role or can perform the mitotic function in the absence of GCN2, we performed live‐cell imaging in the presence of a PERK inhibitor ...