A5039918523- Endoplasmic Reticulum Stress and Disease
- Autophagy in Disease and Therapy
- RNA regulation and disease
- Protein Tyrosine Phosphatases
- Heat shock proteins research
- Ubiquitin and proteasome pathways
- Antibiotic Resistance in Bacteria
- Cystic Fibrosis Research Advances
- Protein Kinase Regulation and GTPase Signaling
- Bacterial biofilms and quorum sensing
- Redox biology and oxidative stress
- RNA Research and Splicing
- Pancreatic function and diabetes
MRC Laboratory of Molecular Biology
2017-2018
Imperial College London
2013-2015
Institute of Structural and Molecular Biology
2013-2014
The unfolded protein response (UPR) is an essential cell signaling system that detects the accumulation of misfolded proteins within endoplasmic reticulum (ER) and initiates a cellular in order to maintain homeostasis. How cells detect remains unclear. In this study, we identify noncanonical interaction between ATPase domain ER chaperone BiP luminal domains UPR sensors Ire1 Perk dissociates when authentic CH1 binds canonical substrate binding BiP. Unlike substrates, found was unaffected by...
Abstract Ire1 is activated in response to accumulation of misfolded proteins within the endoplasmic reticulum as part unfolded protein (UPR). It a unique enzyme, possessing both kinase and RNase activity that required for specific splicing Xbp1 mRNA leading UPR activation. How phosphorylation impacts on unclear. In this study, we isolate distinct phosphorylated species assess their effects vitro vivo . We find activation loop significantly increases vitro. Correspondingly, mutants cannot be...
Protein phosphorylation is a prevalent and ubiquitous mechanism of regulation. Kinases are popular drug targets, but identifying selective phosphatase inhibitors has been challenging. Here, we used surface plasmon resonance to design method enable target-based discovery serine/threonine inhibitors. The targeted regulatory subunit protein 1, PPP1R15B (R15B), negative regulator proteostasis. This yielded Raphin1, inhibitor R15B. In cells, Raphin1 caused rapid transient accumulation its...
Article29 April 2015Open Access Source Data Crystal structures reveal transient PERK luminal domain tetramerization in endoplasmic reticulum stress signaling Marta Carrara Department of Life Sciences, Imperial College, London, UK Search for more papers by this author Filippo Prischi Piotr R Nowak Maruf MU Ali Corresponding Author Information Carrara1,2, Prischi1, Nowak1 and 1 1Department 2Present address: MRC Laboratory Molecular Biology, Francis Crick Avenue, Cambridge, *Corresponding...
The unfolded protein response (UPR) is a cell-signaling system that detects the accumulation of within endoplasmic reticulum (ER) and initiates number cellular responses to restore ER homeostasis. presence detected by ER-luminal sensor domains three UPR-transducer proteins IRE1, PERK, ATF6, which then propagate signal cytosol. In this review, we discuss various mechanisms action have been proposed on how detect activate downstream UPR signaling.
The opportunistic pathogen Pseudomonas aeruginosa chronically infects the airways of Cystic Fibrosis (CF) patients during which it adapts and undergoes clonal expansion within lung. It commonly acquires inactivating mutations anti-sigma factor MucA leading to a mucoid phenotype, caused by excessive production extracellular polysaccharide alginate that is associated with decline in lung function. Alginate believed be key benefit mucA bacterium CF A phenotypic gene expression characterisation...