scholarly journals Cyclophilin A is a mitochondrial factor that forms antiapoptotic complexes with p23

2020 ◽  
Author(s):  
Cristina Daneri-Becerra ◽  
Brenda Valeiras ◽  
Mariana Lagadari ◽  
Mario D. Galigniana
Keyword(s):  
Signal Transduction ◽  
Heat Shock ◽  
Molecular Chaperone ◽  
Intracellular Trafficking ◽  
Functional Unit ◽  
Cyclophilin A ◽  
Cell Types ◽  
Cellular Processes ◽  
Murine Liver ◽  
High Level

AbstractCyclophilin A (CyPA) is an abundant and ubiquitously expressed protein belonging to the immunophilin family that has intrinsic peptidyl-prolyl-(cis/trans)-isomerase enzymatic activity. In addition to mediating the immunosuppressive effects of the drug cyclosporine A, CyPA is involved in multiple cellular processes such as protein folding, intracellular trafficking, signal transduction, and transcriptional regulation. Because CyPA is also a molecular chaperone, its expression is induced by several stressor agents and is a highly abundant protein in cancer cells. In this study, it is demonstrated that in several cell types and at least in murine liver, a significant pool of this immunophilin is primarily an intramitochondrial factor that migrates to the nucleus upon the onset of stress. It is also shown that CyPA has antiapoptotic action. Importantly, the capability of CyPA to form complexes with the small acidic cochaperone p23 is proven, this interaction being independent of the usual association of p23 with the heat-shock protein of 90-kDa, Hsp90. Furthermore, it is demonstrated that the CyPA•p23 complex enhances the antiapoptotic response of the cell, suggesting that both proteins form a functional unit whose high level of expression plays a significant role in cell survival.

scholarly journals Cyclophilin A is a mitochondrial factor that forms complexes with p23. Correlative evidence for an antiapoptotic action

2020 ◽  
pp. jcs.253401
Author(s):  
Cristina Daneri-Becerra ◽  
Brenda Valeiras ◽  
Luciana I. Gallo ◽  
Mariana Lagadari ◽  
Mario D. Galigniana
Keyword(s):  
Signal Transduction ◽  
Heat Shock ◽  
Intracellular Trafficking ◽  
Functional Unit ◽  
Cyclophilin A ◽  
Ternary Complexes ◽  
Cellular Processes ◽  
Immunosuppressive Action ◽  
Per Se ◽  
High Level

Cyclophilin A (CyPA) is an abundant and ubiquitously expressed protein belonging to the immunophilin family that has intrinsic peptidyl-prolyl-(cis/trans)-isomerase enzymatic activity. CyPA mediates immunosuppressive action of the cyclic undecapeptide cyclosporine A and is also involved in multiple cellular processes such as protein folding, intracellular trafficking, signal transduction, and transcriptional regulation. CyPA is abundantly expressed in cancer cells, and due to its chaperone nature, its expression is induced upon the onset of stress. In this study, it is demonstrated that a significant pool of this immunophilin is primarily an intramitochondrial factor that migrates to the nucleus when cells are stimulated with stressors. CyPA shows antiapoptotic action per se and the capability of forming ternary complexes with cytochrome c and the small acidic cochaperone p23, the latter interaction being independent of the usual association of p23 with the heat-shock protein of 90-kDa, Hsp90. These CyPA•p23 complexes enhance the antiapoptotic response of the cell, suggesting that both proteins form a functional unit whose high level of expression plays a significant role in cell survival.

scholarly journals Detecting rare asymmetrically methylated cytosines and decoding methylation patterns in the honeybee genome

2017 ◽  
Vol 4 (9) ◽  
pp. 170248 ◽  
Author(s):  
Laura Welsh ◽  
Ryszard Maleszka ◽  
Sylvain Foret
Keyword(s):  
Cytosine Methylation ◽  
Amplicon Sequencing ◽  
Cell Types ◽  
Cellular Processes ◽  
Novel Approach ◽  
Asymmetric Methylation ◽  
High Level ◽  
Methylation Patterns ◽  
Cg Dinucleotides ◽  
Honeybee Genome

Context-dependent gene expression in eukaryotes is controlled by several mechanisms including cytosine methylation that primarily occurs in the CG dinucleotides (CpGs). However, less frequent non-CpG asymmetric methylation has been found in various cell types, such as mammalian neurons, and recent results suggest that these sites can repress transcription independently of CpG contexts. In addition, an emerging view is that CpG hemimethylation may arise not only from deregulation of cellular processes but also be a standard feature of the methylome. Here, we have applied a novel approach to examine whether asymmetric CpG methylation is present in a sparsely methylated genome of the honeybee, a social insect with a high level of epigenetically driven phenotypic plasticity. By combining strand-specific ultra-deep amplicon sequencing of illustrator genes with whole-genome methylomics and bioinformatics, we show that rare asymmetrically methylated CpGs can be unambiguously detected in the honeybee genome. Additionally, we confirm differential methylation between two phenotypically and reproductively distinct castes, queens and workers, and offer new insight into the heterogeneity of brain methylation patterns. In particular, we challenge the assumption that symmetrical methylation levels reflect symmetry in the underlying methylation patterns and conclude that hemimethylation may occur more frequently than indicated by methylation levels. Finally, we question the validity of a prior study in which most of cytosine methylation in this species was reported to be asymmetric.

Purification, crystallization and preliminary X-ray crystallographic studies of S. cerevisiae Hsp40 Sis1

1999 ◽  
Vol 55 (6) ◽  
pp. 1234-1236 ◽  
Author(s):  
Bingdong Sha ◽  
Douglas Cyr
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Atpase Activity ◽  
Molecular Chaperone ◽  
Molecular Chaperones ◽  
Heat Shock Protein 70 ◽  
Peptide Binding ◽  
X Ray ◽  
Cellular Processes

Heat-shock protein 70 (Hsp70), one of the major molecular chaperones, has been shown to play a central role in many cellular processes. Heat-shock protein 40 (Hsp40) works as a co-chaperone for Hsp70. Hsp40, bound by unfolded polypeptide, can interact directly with Hsp70 to stimulate the ATPase activity of Hsp70. Hsp40 can also bind to unfolded polypeptides and prevent them from aggregating in vitro, thus acting as an independent molecular chaperone. The S. cerevisiae Hsp40 Sis1 C-terminal peptide-binding domain has been crystallized. The crystals diffract to 2.7 Å and belong to space group P41212 or P43212 with a = 73.63, c = 80.16 Å. The structure determination by the MAD method is under way.

scholarly journals Deubiquitinase MYSM1 in the Hematopoietic System and beyond: A Current Review

2020 ◽  
Vol 21 (8) ◽  
pp. 3007 ◽  
Author(s):  
Amanda Fiore ◽  
Yue Liang ◽  
Yun Hsiao Lin ◽  
Jacky Tung ◽  
HanChen Wang ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Current Knowledge ◽  
Cell Types ◽  
Histone H2a ◽  
Hematopoietic Stem ◽  
Developmental Abnormalities ◽  
Cellular Processes ◽  
Different Cell Types

MYSM1 has emerged as an important regulator of hematopoietic stem cell function, blood cell production, immune response, and other aspects of mammalian physiology. It is a metalloprotease family protein with deubiquitinase catalytic activity, as well as SANT and SWIRM domains. MYSM1 normally localizes to the nucleus, where it can interact with chromatin and regulate gene expression, through deubiquitination of histone H2A and non-catalytic contacts with other transcriptional regulators. A cytosolic form of MYSM1 protein was also recently described and demonstrated to regulate signal transduction pathways of innate immunity, by promoting the deubiquitination of TRAF3, TRAF6, and RIP2. In this work we review the current knowledge on the molecular mechanisms of action of MYSM1 protein in transcriptional regulation, signal transduction, and potentially other cellular processes. The functions of MYSM1 in different cell types and aspects of mammalian physiology are also reviewed, highlighting the key checkpoints in hematopoiesis, immunity, and beyond regulated by MYSM1. Importantly, mutations in MYSM1 in human were recently linked to a rare hereditary disorder characterized by leukopenia, anemia, and other hematopoietic and developmental abnormalities. Our growing knowledge of MYSM1 functions and mechanisms of actions sheds important insights into its role in mammalian physiology and the etiology of the MYSM1-deficiency disorder in human.

scholarly journals The emerging role of phosphoinositide clustering in intracellular trafficking and signal transduction

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 422 ◽  
Author(s):  
Laura Picas ◽  
Frederique Gaits-Iacovoni ◽  
Bruno Goud
Keyword(s):  
Signal Transduction ◽  
Intracellular Trafficking ◽  
Recent Observation ◽  
Metabolizing Enzymes ◽  
Master Regulators ◽  
Cellular Processes ◽  
Cellular Compartments ◽  
Cytoskeleton Dynamics ◽  
Protein Modules

Phosphoinositides are master regulators of multiple cellular processes: from vesicular trafficking to signaling, cytoskeleton dynamics, and cell growth. They are synthesized by the spatiotemporal regulated activity of phosphoinositide-metabolizing enzymes. The recent observation that some protein modules are able to cluster phosphoinositides suggests that alternative or complementary mechanisms might operate to stabilize the different phosphoinositide pools within cellular compartments. Herein, we discuss the different known and potential molecular players that are prone to engage phosphoinositide clustering and elaborate on how such a mechanism might take part in the regulation of intracellular trafficking and signal transduction.

scholarly journals Mitochondrial Glucocorticoid Receptors and Their Actions

2021 ◽  
Vol 22 (11) ◽  
pp. 6054
Author(s):  
Ioanna Kokkinopoulou ◽  
Paraskevi Moutsatsou
Keyword(s):  
Gene Expression ◽  
Glucocorticoid Receptors ◽  
Mitochondrial Gene ◽  
Cell Types ◽  
Ros Generation ◽  
Mitochondrial Gene Expression ◽  
Mitochondrial Energy Metabolism ◽  
Bcl2 Family ◽  
Cellular Processes ◽  
Almost All

Mitochondria are membrane organelles present in almost all eukaryotic cells. In addition to their well-known role in energy production, mitochondria regulate central cellular processes, including calcium homeostasis, Reactive Oxygen Species (ROS) generation, cell death, thermogenesis, and biosynthesis of lipids, nucleic acids, and steroid hormones. Glucocorticoids (GCs) regulate the mitochondrially encoded oxidative phosphorylation gene expression and mitochondrial energy metabolism. The identification of Glucocorticoid Response Elements (GREs) in mitochondrial sequences and the detection of Glucocorticoid Receptor (GR) in mitochondria of different cell types gave support to hypothesis that mitochondrial GR directly regulates mitochondrial gene expression. Numerous studies have revealed changes in mitochondrial gene expression alongside with GR import/export in mitochondria, confirming the direct effects of GCs on mitochondrial genome. Further evidence has made clear that mitochondrial GR is involved in mitochondrial function and apoptosis-mediated processes, through interacting or altering the distribution of Bcl2 family members. Even though its exact translocation mechanisms remain unknown, data have shown that GR chaperones (Hsp70/90, Bag-1, FKBP51), the anti-apoptotic protein Bcl-2, the HDAC6- mediated deacetylation and the outer mitochondrial translocation complexes (Tom complexes) co-ordinate GR mitochondrial trafficking. A role of mitochondrial GR in stress and depression as well as in lung and hepatic inflammation has also been demonstrated.

High level soluble expression and ATPase characterization of human heat shock protein GRP78

2017 ◽  
Vol 82 (2) ◽  
pp. 186-191
Author(s):  
Shuang Wu ◽  
Hongpeng Zhang ◽  
Miao Luo ◽  
Ke Chen ◽  
Wei Yang ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Soluble Expression ◽  
High Level ◽  
Human Heat Shock Protein
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