Background: ADP-ribosylation is a ubiquitous post-translational modification that involves both mono- and poly-ADP-ribosylation. ARTD10, also known as PARP10, mediates mono-ADP-ribosylation (MARylation) of substrate proteins. A previous screen identified protein kinase C delta (PKCδ) as a potential ARTD10 substrate, among several other kinases. The voltage-gated K channel Kv1.1 constitutes one of the dominant Kv channels in neurons of the central nervous system and the inactivation properties of Kv1.1 are modulated by PKC. In this study, we addressed the role of ARTD10-PKCδ as a regulator of Kv1.1.
Results: We found that ARTD10 inhibited PKCδ, which increased Kv1.1 current amplitude and the proportion of the inactivating current component in HeLa cells, indicating that ARTD10 regulates Kv1.1 in living cells. An inhibitor of ARTD10, OUL35, significantly decreased peak amplitude together with the proportion of the inactivating current component of Kv1.1-containing channels in primary hippocampal neurons, demonstrating that the ARTD10-PKCδ signaling cascade regulates native Kv1.1. Moreover, we show that the pharmacological blockade of ARTD10 increases excitability of hippocampal neurons.
Conclusions: Our results, for the first time, suggest that MARylation by ARTD10 controls neuronal excitability.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558731 | PMC |
| http://dx.doi.org/10.1186/s12915-020-00878-1 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
PARP10 Multi-Site Auto- and Histone MARylation Visualized by Acid-Urea Gel Electrophoresis.
Cells
March 2021
Department of Biosciences and Nutrition, Karolinska Institutet, 14157 Huddinge, Sweden.
Poly-ADP-ribose polymerase (PARP)-family ADP-ribosyltransferases function in various signaling pathways, predominantly in the nucleus and cytosol. Although PARP inhibitors are in clinical practice for cancer therapy, the enzymatic activities of individual PARP family members are yet insufficiently understood. We studied PARP10, a mono-ADP-ribosyltransferase and potential drug target.
View Article and Find Full Text PDFMono(ADP-ribosyl)ation Enzymes and NAD Metabolism: A Focus on Diseases and Therapeutic Perspectives.
Cells
January 2021
Institute for the Experimental Endocrinology and Oncology, National Research Council of Italy, Via Tommaso de Amicis 95, 80145 Naples, Italy.
Mono(ADP-ribose) transferases and mono(ADP-ribosyl)ating sirtuins use NAD to perform the mono(ADP-ribosyl)ation, a simple form of post-translational modification of proteins and, in some cases, of nucleic acids. The availability of NAD is a limiting step and an essential requisite for NAD consuming enzymes. The synthesis and degradation of NAD, as well as the transport of its key intermediates among cell compartments, play a vital role in the maintenance of optimal NAD levels, which are essential for the regulation of NAD-utilizing enzymes.
View Article and Find Full Text PDFThe mono-ADP-ribosyltransferase ARTD10 regulates the voltage-gated K channel Kv1.1 through protein kinase C delta.
BMC Biol
October 2020
Institute of Physiology, RWTH Aachen University, Pauwelsstrasse 30, 52074, Aachen, Germany.
Background: ADP-ribosylation is a ubiquitous post-translational modification that involves both mono- and poly-ADP-ribosylation. ARTD10, also known as PARP10, mediates mono-ADP-ribosylation (MARylation) of substrate proteins. A previous screen identified protein kinase C delta (PKCδ) as a potential ARTD10 substrate, among several other kinases.
View Article and Find Full Text PDFPARP10 (ARTD10) modulates mitochondrial function.
PLoS One
February 2018
Department of Medical Chemistry, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
Article Synopsis
- PARP10 is a member of the PARP family known for its role in mono-ADP-ribosylation of proteins and has been linked to metabolic processes.
- Silencing PARP10 in cancer cell models led to enhanced mitochondrial oxidative capacity, reduced oxidative stress, and greater expression of antioxidant genes, resulting in decreased cell proliferation.
- Lower expression of PARP10 is associated with improved survival rates in gastric cancer and is influenced by metabolic conditions like fasting, which promotes mitochondrial biogenesis and fatty acid oxidation.
Small-Molecule Chemical Probe Rescues Cells from Mono-ADP-Ribosyltransferase ARTD10/PARP10-Induced Apoptosis and Sensitizes Cancer Cells to DNA Damage.
Cell Chem Biol
October 2016
Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Oulu 90014, Finland. Electronic address:
Members of the human diphtheria toxin-like ADP-ribosyltransferase (ARTD or PARP) family play important roles in regulating biological activities by mediating either a mono-ADP-ribosylation (MARylation) of a substrate or a poly-ADP-ribosylation (PARylation). ARTD10/PARP10 belongs to the MARylating ARTDs (mARTDs) subfamily, and plays important roles in biological processes that range from cellular signaling, DNA repair, and cell proliferation to immune response. Despite their biological and disease relevance, no selective inhibitors for mARTDs are available.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!