Lysine trimethylation regulates 78-kDa glucose-regulated protein proteostasis during endoplasmic reticulum stress

Sieber, Jonas; Wieder, Nicolas; Ostrosky-Frid, Mauricio; Dvela‐Levitt, Moran; Aygün, Ozan; Udeshi, Namrata D.; Carr, Steven A.; Greka, Anna

doi:10.1074/jbc.m117.797084

Cited by 12 publications

(11 citation statements)

References 26 publications

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“…Hsc70 Lys-561 and the orthogonal residues in BiP, Hsp70, HSPA2/Hsp70-2, and HSPA6/Hsp70B9 are trimethylated by the nonhistone methylase METTL21A (134,136,137,142). In the presence of ER stress, BiP K586me3 is degraded by the lysosome and replaced with methyl-free de novo translated BiP, implicating a role for K586me3 in the regulation of BiP's chaperoning function (143). Hsc70 Lys-561 trimethylation affects its ability to bind to substrates, such as a-synuclein (136).…”

Section: Hsp70 Methylation In Direct Regulation Of Chaperoning Functionmentioning

confidence: 99%

“…One is that they are separate proteins in separate subcellular compartments, and so this same modification may play different roles in specific contexts. Additionally, BiP K586me3 is degraded following ER stress, as are several other ER-resident chaperones (143). Finally, the stabilizing effects of Hsc70 K561me3 were studied using a lysine-to-arginine mutation to mimic lysine methylation (144).…”

Section: Hsp70 Methylation In Direct Regulation Of Chaperoning Functionmentioning

confidence: 99%

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Post-translational modifications of Hsp70 family proteins: Expanding the chaperone code

Nitika

Porter

Truman

et al. 2020

Journal of Biological Chemistry

119

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Cells must be able to cope with the challenge of folding newly synthesized proteins and refolding those that have become misfolded in the context of a crowded cytosol. One such coping mechanism that has appeared during evolution is the expression of well-conserved molecular chaperones, such as those that are part of the heat shock protein 70 (Hsp70) family of proteins that bind and fold a large proportion of the proteome. Although Hsp70 family chaperones have been extensively examined for the last 50 years, most studies have focused on regulation of Hsp70 activities by altered transcription, co-chaperone “helper” proteins, and ATP binding and hydrolysis. The rise of modern proteomics has uncovered a vast array of post-translational modifications (PTMs) on Hsp70 family proteins that include phosphorylation, acetylation, ubiquitination, AMPylation, and ADP-ribosylation. Similarly to the pattern of histone modifications, the histone code, this complex pattern of chaperone PTMs is now known as the “Chaperone Code.” In this review, we discuss the history of the Hsp70 chaperone code, its currently understood regulation and functions, as well as thoughts on what the future of research into the chaperone code may entail.

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Section: Hsp70 Methylation In Direct Regulation Of Chaperoning Functionmentioning

confidence: 99%

Section: Hsp70 Methylation In Direct Regulation Of Chaperoning Functionmentioning

confidence: 99%

Post-translational modifications of Hsp70 family proteins: Expanding the chaperone code

Nitika

Porter

Truman

et al. 2020

Journal of Biological Chemistry

119

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“…As a chaperone protein, it plays an essential role in helping proteins fold correctly and in the process of degrading the wrong proteins [29,30]. Some [31]. In our experiment, one BIP gene was downregulated in Guangdong snails.…”

Section: Candidate Cold-resistance Genes Related To Homeostasismentioning

confidence: 52%

“…As a chaperone protein, it plays an essential role in helping proteins fold correctly and in the process of degrading the wrong proteins [ 29 , 30 ]. Some reports have pointed out that the upregulation of the BIP chaperone protein is part of the adaptive cellular response to ER stress [ 31 ]. In our experiment, one BIP gene was downregulated in Guangdong snails.…”

Section: Discussionmentioning

confidence: 99%

A Comparative Transcriptomics Approach to Analyzing the Differences in Cold Resistance in Pomacea canaliculata between Guangdong and Hunan

Liu

Sun

Wang

et al. 2020

Journal of Immunology Research

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Pomacea canaliculata, known as an invasive freshwater snail, is also called a golden apple snail; its survival and expansion are greatly affected by temperature. In this study, high-throughput sequencing (RNA-seq) was used to perform comparative transcriptome analysis on the muscular tissue (G_M) of snails in Guangdong and Hunan. Differential gene screening was performed with FDR <0.05 and |log2FoldChange| >1 as the threshold, and a total of 1,368 differential genes were obtained (671 genes showed upregulation in snails from Guangdong, and 697 genes displayed upregulation in snails from Hunan). Fifteen genes were identified as candidate genes for the cold hardiness of Pomacea canaliculata. Among them, three genes were involved in energy metabolism (glycogen synthase, 1; DGK, 1; G6PD, 1); seven genes were involved in homeostasis regulation (HSP70, 2; BIP, 1; GPX, 1; GSTO 1, G6PD, 1; caspase-9, 1); two genes were involved in amino acid metabolism (glutamine synthetase, 1; PDK, 1); and four genes were involved in membrane metabolism (inositol-3-phosphate synthase, 1; Na+/K+-ATPase, 1; calcium-binding protein, 2). This study presents the molecular mechanisms for the cold hardiness of Pomacea canaliculata, which could provide a scientific basis for the forecast and prevention of harm from Pomacea canaliculata.

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“…ER stress led to de novo biosynthesis of non-trimethylated GRP78, whereas homeostatic, N-lysine methyltransferase 21A (METTL21A)-dependent lysine 585-trimethylated GRP78 was reduced. ER stress triggered the de novo synthesis of non-trimethylated GRP78 and simultaneous degradation of existing, lysine-trimethylated GRP78 [44]. This previously unrecognized mechanism suggests the lack of posttranslational modification may alter the conformation of GRP78 in a way that may be beneficial during ER stress to secure cell survival.…”

Section: Epigenetic Regulation Of the Uprmentioning

confidence: 99%

Unfolded Protein Response and Crohn’s Diseases: A Molecular Mechanism of Wound Healing in the Gut

Li¹

2020

Preprint

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Endoplasmic reticulum (ER) stress triggers a series of signaling and transcriptional events termed the unfolded protein response (UPR). Severe ER stress is associated with the development of fibrosis in different organs including lung, liver, kidney, heart, and intestine. ER stress is an essential response of epithelial and immune cells in the pathogenesis of inflammatory bowel disease (IBD) including Crohn’s disease. Intestinal epithelial cells are susceptible to ER stress-mediated damage due to secretion of a large amount of proteins that are involved in mucosal defense. In other cells, ER stress is linked to myofibroblast activation, extracellular matrix production, macrophage polarization, and immune cell differentiation. This review focuses on the role of UPR in the pathogenesis in IBD from immunologic perspective. The roles of macrophage and mesenchymal cells in the UPR from in vitro and in vivo animal models are discussed. The links between ER stress and other signaling pathways such as senescence and autophagy are introduced. Recent advances in the understanding of the epigenetic regulation of UPR signaling are reported. The future directions of the development of the UPR research and therapeutic strategies to manipulate ER stress levels are also reviewed.

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Lysine trimethylation regulates 78-kDa glucose-regulated protein proteostasis during endoplasmic reticulum stress

Cited by 12 publications

References 26 publications

Post-translational modifications of Hsp70 family proteins: Expanding the chaperone code

Post-translational modifications of Hsp70 family proteins: Expanding the chaperone code

A Comparative Transcriptomics Approach to Analyzing the Differences in Cold Resistance in Pomacea canaliculata between Guangdong and Hunan

Unfolded Protein Response and Crohn’s Diseases: A Molecular Mechanism of Wound Healing in the Gut

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