PARP14 mediated SQSTM1/p62 cysteine ADP-ribosylation is counteracted by the SARS-CoV-2 macrodomain
Kubon, D.; Leslie Pedrioli, D. M.; Hottiger, M. O.
Show abstract
Several ADP-ribosyltransferases are upregulated during viral infections and are crucial for the cellular immune response. While interferon-induced PARP14 ADP-ribosylates various substrates, viruses such as SARS-CoV-2 counteract this by reversing ADP-ribosylation. The exact mechanism of PARP14s antiviral activity and the targets of viral macrodomains remain unknown. Here, we observe that PARP14 mono-ADP-ribosylates the selective autophagy adaptor SQSTM1/p62 at cysteine residues 113, 289/90, and 331 following interferon treatment. This correlates with the ADP-ribosylation of cytoplasmic p62 foci that colocalize with ubiquitin and PARP14 but not with LC3, thereby distinguishing them from classical autophagosomes. Moreover, the SARS-CoV-2 macrodomain effectively prevented this p62 modification, suggesting an antiviral function for this ADP-ribosylated target. Furthermore, our results indicate that TRIM21 prevents the autophagic degradation of ADP-ribosylated p62, suggesting that the identified p62 foci may have autophagy-independent roles. This study contributes to our understanding of the molecular dynamics involved in host-virus interactions and highlights the potential role of ADP-ribosylation in the regulation of innate immunity.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Proximal protein landscapes of the type I interferon signaling cascade reveal negative regulation by the E3 ubiquitin ligase PJA2 96%
- Mitochondrial protein C15ORF48 is a stress-independent inducer of autophagy that regulates oxidative stress and autoimmunity 95%
- GAK and PRKCD are positive regulators of PRKN-independent mitophagy 95%
Similar papers in this journal
- The evolutionarily conserved PRP4K-CHMP4B/vps32 splicing circuit regulates autophagy 94%
- Interactomic analysis reveals a new homeostatic role for the HIV restriction factor TRIM5α in mitophagy 94%
- PERK-dependent reciprocal crosstalk between ER and non-centrosomal microtubules coordinates ER architecture and cell shape 94%
Similar papers in this journal
- TNIP1 inhibits Mitophagy via interaction with FIP200 and TAX1BP1 95%
- ADAR1p150 Prevents MDA5 and PKR Activation via Distinct Mechanisms to Avert Fatal Autoinflammation 94%
- RAPIDASH: A tag-free enrichment of ribosome-associated proteins reveals compositional dynamics in embryonic tissues and stimulated macrophages 94%
Similar papers in this journal
- Genome-Wide CRISPR Screening Identifies BRD9 as a Druggable Component of Interferon-Stimulated Gene Expression and Antiviral Activity 94%
- Parkin coordinates mitochondrial lipid remodeling to execute mitophagy 94%
- Drs2 regulates TRAPPIII in Atg9 transport: exposing the interplay of P4-ATPases and Multisubunit Tethering Complexes 93%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.