Cyclosporin A but not FK506 activates the integrated stress response in human cells [Cell Biology]
Cyclosporin A (CsA) and tacrolimus (FK506) are valuable immunosuppressants for a range of clinical settings, including (but not limited to) organ transplantation and the treatment of autoimmune diseases. They function by inhibiting the activity of the Ca2+/calmodulin-dependent phosphatase calcineurin toward nuclear factor of activated T-cells (NF-AT) in T-lymphocytes. However, use of CsA is associated with more serious side effects and worse clinical outcomes than FK506. Here we show that CsA, but not FK506, causes activation of the integrated stress response (ISR), an event which is normally an acute reaction to various t...
Source: Journal of Biological Chemistry - October 30, 2020 Category: Chemistry Authors: Anthony O. Fedele, Valerie Carraro, Jianling Xie, Julien Averous, Christopher G. Proud Tags: Signal Transduction Source Type: research
Differential processing and localization of human Nocturnin controls metabolism of mRNA and nicotinamide adenine dinucleotide cofactors [Metabolism]
In this study, we analyze the expression, processing, localization, and cellular functions of human NOCT. We find that NOCT protein is differentially expressed and processed in a cell and tissue type–specific manner to control its localization to the cytoplasm or mitochondrial exterior or interior. The N terminus of NOCT is necessary and sufficient to confer import and processing in the mitochondria. We measured the impact of cytoplasmic NOCT on the transcriptome and observed that it affects mRNA levels of hundreds of genes that are significantly enriched in osteoblast, neuronal, and mitochondrial functions. Recent bioch...
Source: Journal of Biological Chemistry - October 30, 2020 Category: Chemistry Authors: Elizabeth T. Abshire, Kelsey L. Hughes, Rucheng Diao, Sarah Pearce, Shreekara Gopalakrishna, Raymond C. Trievel, Joanna Rorbach, Peter L. Freddolino, Aaron C. Goldstrohm Tags: RNA Source Type: research
Amyloid-{beta} regulates gap ȷunction protein connexin 43 trafficking in cultured primary astrocytes [Molecular Bases of Disease]
Altered expression and function of astroglial gap junction protein connexin 43 (Cx43) has increasingly been associated to neurotoxicity in Alzheimer disease (AD). Although earlier studies have examined the effect of increased β-amyloid (Aβ) on Cx43 expression and function leading to neuronal damage, underlying mechanisms by which Aβ modulates Cx43 in astrocytes remain elusive. Here, using mouse primary astrocyte cultures, we have examined the cellular processes by which Aβ can alter Cx43 gap junctions. We show that Aβ25-35 impairs functional gap junction coupling yet increases hemichannel activity. Interestingly, Aβ2...
Source: Journal of Biological Chemistry - October 30, 2020 Category: Chemistry Authors: Mahua Maulik, Lakshmy Vasan, Abhishek Bose, Saikat Dutta Chowdhury, Neelanjana Sengupta, Jayasri Das Sarma Tags: Neurobiology Source Type: research
Solid-state NMR spectroscopy identifies three classes of lipids in Cryptococcus neoformans melanized cell walls and whole fungal cells [Microbiology]
A primary virulence-associated trait of the opportunistic fungal pathogen Cryptococcus neoformans is the production of melanin pigments that are deposited into the cell wall and interfere with the host immune response. Previously, our solid-state NMR studies of isolated melanized cell walls (melanin “ghosts”) revealed that the pigments are strongly associated with lipids, but their identities, origins, and potential roles were undetermined. Herein, we exploited spectral editing techniques to identify and quantify the lipid molecules associated with pigments in melanin ghosts. The lipid profiles were remarkably similar ...
Source: Journal of Biological Chemistry - October 30, 2020 Category: Chemistry Authors: Christine Chrissian, Emma Camacho, John E. Kelly, Hsin Wang, Arturo Casadevall, Ruth E. Stark Tags: Molecular Biophysics Source Type: research
A ubiquitin variant-based affinity approach selectively identifies substrates of the ubiquitin ligase E6AP in complex with HPV-11 E6 or HPV-16 E6 [Protein Synthesis and Degradation]
In conclusion, our data represent a reliable repository for potential substrates of the HPV-16 and HPV-11 E6 proteins in complex with E6AP. (Source: Journal of Biological Chemistry)
Source: Journal of Biological Chemistry - October 30, 2020 Category: Chemistry Authors: Felix A. Ebner, Carolin Sailer, Daniela Eichbichler, Jasmin Jansen, Anna Sladewska-Marquardt, Florian Stengel, Martin Scheffner Tags: Protein Synthesis and Degradation Source Type: research
