scholarly journals Reversible ADP-ribosylation of RNA

2019 ◽  
Vol 47 (11) ◽  
pp. 5658-5669 ◽  
Author(s):  
Deeksha Munnur ◽  
Edward Bartlett ◽  
Petra Mikolčević ◽  
Ilsa T Kirby ◽  
Johannes Gregor Matthias Rack ◽  
...  
Keyword(s):  
Dna Repair ◽  
Stress Response ◽  
Nicotinamide Adenine Dinucleotide ◽  
Cellular Stress Response ◽  
Biological Processes ◽  
Adp Ribosylation ◽  
Human Proteins ◽  
Novel Target ◽  
Host Virus Interactions ◽  
Virus Interactions

Abstract ADP-ribosylation is a reversible chemical modification catalysed by ADP-ribosyltransferases such as PARPs that utilize nicotinamide adenine dinucleotide (NAD+) as a cofactor to transfer monomer or polymers of ADP-ribose nucleotide onto macromolecular targets such as proteins and DNA. ADP-ribosylation plays an important role in several biological processes such as DNA repair, transcription, chromatin remodelling, host-virus interactions, cellular stress response and many more. Using biochemical methods we identify RNA as a novel target of reversible mono-ADP-ribosylation. We demonstrate that the human PARPs - PARP10, PARP11 and PARP15 as well as a highly diverged PARP homologue TRPT1, ADP-ribosylate phosphorylated ends of RNA. We further reveal that ADP-ribosylation of RNA mediated by PARP10 and TRPT1 can be efficiently reversed by several cellular ADP-ribosylhydrolases (PARG, TARG1, MACROD1, MACROD2 and ARH3), as well as by MACROD-like hydrolases from VEEV and SARS viruses. Finally, we show that TRPT1 and MACROD homologues in bacteria possess activities equivalent to the human proteins. Our data suggest that RNA ADP-ribosylation may represent a widespread and physiologically relevant form of reversible ADP-ribosylation signalling.

Cellular Stress Response: A Novel Target for Chemoprevention and Nutritional Neuroprotection in Aging, Neurodegenerative Disorders and Longevity

2008 ◽  
Vol 33 (12) ◽  
pp. 2444-2471 ◽  
Author(s):  
Vittorio Calabrese ◽  
Carolin Cornelius ◽  
Cesare Mancuso ◽  
Giovanni Pennisi ◽  
Stella Calafato ◽  
...  
Keyword(s):  
Stress Response ◽  
Neurodegenerative Disorders ◽  
Cellular Stress ◽  
Cellular Stress Response ◽  
Novel Target

scholarly journals Glycosyltransferases encoded by viruses

2004 ◽  
Vol 85 (10) ◽  
pp. 2741-2754 ◽  
Author(s):  
Nicolas Markine-Goriaynoff ◽  
Laurent Gillet ◽  
James L. Van Etten ◽  
Haralambos Korres ◽  
Naresh Verma ◽  
...  
Keyword(s):  
Evolution Process ◽  
Cellular Biology ◽  
Biological Processes ◽  
Virally Encoded ◽  
Host Virus Interactions ◽  
Virus Interactions

Studies of cellular biology in recent decades have highlighted the crucial roles of glycans in numerous important biological processes, raising the concept of glycomics that is now considered as important as genomics, transcriptomics and proteomics. For millions of years, viruses have been co-evolving with their hosts. Consequently, during this co-evolution process, viruses have acquired mechanisms to mimic, hijack or sabotage host processes that favour their replication, including mechanisms to modify the glycome. The importance of the glycome in the regulation of host–virus interactions has recently led to a new concept called ‘glycovirology’. One fascinating aspect of glycovirology is the study of how viruses affect the glycome. Viruses reach that goal either by regulating expression of host glycosyltransferases or by expressing their own glycosyltransferases. This review describes all virally encoded glycosyltransferases and discusses their established or putative functions. The description of these enzymes illustrates several intriguing aspects of virology and provides further support for the importance of glycomics in biological processes.

scholarly journals Multiplexed phospholipid membrane platform for curvature sensitive protein screening

Nanoscale ◽  
2021 ◽  
Author(s):  
Eider Berganza Eguiarte ◽  
Mirsana Ebrahimkutty ◽  
Srivatsan Vasantham ◽  
Chunting Zhong ◽  
Alexander Wunsch ◽  
...  
Keyword(s):  
Membrane Trafficking ◽  
Lipid Membranes ◽  
Membrane Curvature ◽  
In Vitro Studies ◽  
Biological Processes ◽  
Phospholipid Membrane ◽  
Host Virus Interactions ◽  
Virus Interactions

The curvature of lipid membranes plays a key role in many relevant biological processes such as membrane trafficking, vesicular budding or host-virus interactions. In-vitro studies on membrane curvature of simplified...

scholarly journals DDRE-06. CELLULAR STRESS RESPONSE IN DIPG THERAPY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii62-ii62
Author(s):  
Sreepradha Sridharan ◽  
Arif Harmanci ◽  
Robert Siddaway ◽  
Tara Dobson ◽  
Jyothishmathi Swaminathan ◽  
...  
Keyword(s):  
Stress Response ◽  
Single Cell ◽  
Synthetic Lethality ◽  
Clonal Evolution ◽  
Single Agent ◽  
Objective Response ◽  
Hdac Inhibitors ◽  
Pediatric Brain Tumor ◽  
Dominant Negative ◽  
Cellular Stress Response

Abstract Diffuse Intrinsic Pontine Glioma (DIPG) is an incurable pediatric brain tumor of the pons and brainstem. Therefore, there is a desperate need for new therapeutics. Genomic profiling of tumors identified a highly prevalent dominant negative somatic mutation at lysine (K)-27 in histone genes HIST1H3B and H3F3A. Clonal evolution modeling suggests these mutations are truncal, and studies have demonstrated their contribution to tumorigenesis. ONC201, a first-in-class DRD2 antagonist and ClpP agonist is an anticancer drug developed by Oncoceutics, which targets the unfolded protein response (UPR) and integrated stress response (ISR) signaling and is actively being investigated in patients with recurrent H3 K27M-mutant gliomas. In adults with recurrent glioma, single agent studies showed benign-safety, no dose-limiting toxicities and a durable objective response when administered orally. In addition, intra-tumoral drug levels exceeded therapeutic thresholds, and induced tumor cell apoptosis. Based on this and response seen in a pediatric patient with DIPG for whom compassionate use of ONC201 was approved, a multi-arm, non-randomized multi-institutional Phase I clinical trial (NCT03416530) is actively accruing patients. However, the strength of UPR and ISR in DIPGs and their effect on DIPG response to ONC201 is not known. Our group employed bulk/single cell transcriptomic and single cell proteomic approaches to demonstrate substantial heterogeneity in UPR and ISR signaling in human DIPG samples. Consistent with this, DIPG cell lines exhibited considerable variability in sensitivity to ONC201. Single cell profiling identified tumor sub-populations with significant proliferative capacity even after ONC201 exposure. Incomplete response promotes recurrence. To target these cells, we performed a synthetic lethality screen with a library of 360 FDA-approved CNS penetrant compounds, which identified HDAC inhibitors and DNA damage-inducing chemotherapy as having synergy with ONC201. Thus, we suggest that tumor heterogeneity impacts sensitivity to ONC201 and that this can be reduced by combination treatments.

scholarly journals Flavonoids: Potential Candidates for the Treatment of Neurodegenerative Disorders

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 99
Author(s):  
Shweta Devi ◽  
Vijay Kumar ◽  
Sandeep Kumar Singh ◽  
Ashish Kant Dubey ◽  
Jong-Joo Kim
Keyword(s):  
Stress Response ◽  
Stress Responses ◽  
Neurodegenerative Disorders ◽  
Cell Damage ◽  
Cellular Stress ◽  
Clinical Manifestations ◽  
Cellular Stress Response ◽  
Dramatic Rise ◽  
Cellular Stress Responses

Neurodegenerative disorders, such as Parkinson’s disease (PD), Alzheimer’s disease (AD), Amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD), are the most concerning disorders due to the lack of effective therapy and dramatic rise in affected cases. Although these disorders have diverse clinical manifestations, they all share a common cellular stress response. These cellular stress responses including neuroinflammation, oxidative stress, proteotoxicity, and endoplasmic reticulum (ER)-stress, which combats with stress conditions. Environmental stress/toxicity weakened the cellular stress response which results in cell damage. Small molecules, such as flavonoids, could reduce cellular stress and have gained much attention in recent years. Evidence has shown the potential use of flavonoids in several ways, such as antioxidants, anti-inflammatory, and anti-apoptotic, yet their mechanism is still elusive. This review provides an insight into the potential role of flavonoids against cellular stress response that prevent the pathogenesis of neurodegenerative disorders.

scholarly journals Mitochondrien unter Stress: Die Rolle der Präsequenzprotease MPP

BIOspektrum ◽  
2021 ◽  
Vol 27 (4) ◽  
pp. 390-393
Author(s):  
F.-Nora Vögtle
Keyword(s):  
Stress Response ◽  
Cellular Stress ◽  
Critical Role ◽  
Mitochondrial Protein ◽  
Nuclear Genome ◽  
Cellular Stress Response ◽  
Mitochondrial Proteins ◽  
Protein Biogenesis ◽  
Cellular Integrity

AbstractThe majority of mitochondrial proteins are encoded in the nuclear genome, so that the nearly entire proteome is assembled by post-translational preprotein import from the cytosol. Proteomic imbalances are sensed and induce cellular stress response pathways to restore proteostasis. Here, the mitochondrial presequence protease MPP serves as example to illustrate the critical role of mitochondrial protein biogenesis and proteostasis on cellular integrity.

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