Importance of Deubiquitination in Macrophage-Mediated Viral Response and Inflammation
Abstract
:1. Introduction
2. Ubiquitination and Deubiquitination in the RLR Pathway
2.1. K63-Linked Ubiquitination: RIG-I Activation and Cytosolic Warriors
2.2. K48-Linked Ubiquitination: RIG-I Degradation
2.3. Deubiquitination: Negative Regulators of RIG-I
2.3.1. CYLD
2.3.2. A20
2.3.3. USP21
2.3.4. USP3
2.3.5. USP15
2.3.6. USP25
2.3.7. USP14
2.3.8. USP18
2.4. Positive Regulators of RIG-I
USP4 and USP17
3. Ubiquitination and Deubiquitination in TLR Signaling
3.1. Ubiquitination of TLR Signaling Molecules: TRAF3, TRAF6, TBK1, RIP1, TAK1
3.2. Deubiquitination of TLR Signaling Molecules
3.2.1. USP2/USP2a
3.2.2. USP4
3.2.3. USP7
3.2.4. USP10
3.2.5. USP18
3.2.6. USP25
3.2.7. USP12
3.2.8. A20
3.2.9. CYLD
3.2.10. MYSM1
4. Ubiquitination in NLR Signaling
4.1. Ubiquitination of NLRP3 and RIP2
4.2. Deubiquitination of NLR Signaling Molecules
4.2.1. A20
4.2.2. BRCC3
4.2.3. USP7 and USP47
5. DUB Inhibitors
5.1. DUB Inhibitor (WP1130) for Bacterial Killing in Macrophages
5.2. DUB Inhibitors in Inflammasome Assembly
6. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
PRR | Pattern recognition receptors |
PAMPS | Pathogen-associated molecular patterns |
DAMPS | Danger-associated molecular patterns |
DUB | Deubiquitinating enzyme |
KC | Kupffer cell |
TLR | Toll-like receptors |
RIG-I | Retinoic acid-inducible gene I |
RLR | RIG-I- like receptors |
MDA5 | Melanoma-differentiation-associated gene 5 |
NOD | Nucleotide-binding oligomerization domain |
NLR | NOD-like receptors |
IFN | Interferons |
IL | Interleukin |
AIM2 | Absent in melanoma 2 |
NLRP3 | Nucleotide-binding oligomerization domain leucine-rich repeat and pyrin domain-containing protein 3 |
ASC | Apoptosis-associated speck-like protein containing a caspase activating and recruitment domain |
CARD | Caspase activation and recruitment domains |
VSV | Vesicular stomatitis virus |
TRIM25 | Tripartite motif containing 25 |
MAVS | Mitochondrial antiviral-signaling protein |
NF-κB | Nuclear factor-κB |
TRAF | Tumor necrosis factor receptor-associated factor |
IKK | Inhibitor of nuclear factor κB kinase |
TBK1 | Tank-binding kinase 1 |
IRF | IFN regulatory factor |
CHIP | C-terminus of Hsc70 interacting protein |
RNF | RING-finger protein |
STING | Stimulator of IFN genes |
LUBAC | Linear ubiquitin assembly complex |
TAX1BP1 | Tax1-binding protein 1 |
ISRE | IFN-stimulated response element |
MyD88 | Myeloid differentiation primary response 88 |
TIR | Toll/Interleukin-1 receptor |
TRIF | TIR-domain-containing adapter-inducing interferon-β |
IRAK | IL-1R-associated serine/threonine kinases |
TNFR1 | TNF receptor-1 |
EV71 | Enterovirus 71 |
MNV 1 | Murine norovirus 1 |
FBXO3 | F-box protein 3 |
BRCC3 | BRCA1/BRCA2-containing complex 3 |
BRISC | BRCC36 isopeptidase complex |
EMPs | Erythromyeloid progenitors |
HSCs | Hematopoietic stem cells |
IPS-1 | Interferon-beta promoter stimulator 1 |
ISG | Interferon stimulating genes |
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Pathway | DUBs | Target | Mechanism | Reference |
---|---|---|---|---|
RLR | CYLD | RIG-I, MAVS, TBK1, IKKε, TRAF2, TRAF3, TRAF6 | Deubiquitinates K63-Ub chain | [41,44,90,110,111] |
A20 | TBK1, IKKi, TRAF6, IRF7 | Deubiquitinates K63-Ub chain | [47,90,112] | |
USP21 | RIG-I, MDA5 | Deubiquitinates K63-Ub chain, Inhibits TRIM25 and RNF135 | [51,52] | |
USP3 | RIG-I, MDA5 | Deubiquitinates K63-Ub chain | [53] | |
USP15 | RIG-I | Deubiquitinates K63-Ub chain | [54,55] | |
USP25 | RIG-I, TRAF2, TRAF3, TRAF6 | Deubiquitinates K63-Ub chain from RIG-I and TRAF6, Deubiquitinates K48-Ub chain from TRAF3 | [57,58] | |
USP14 | RIG-I | Deubiquitinates K63-Ub chain | [59] | |
USP18 | TAK1, NEMO | Recruits USP20 to deconjugate K48-Ub chain from STING | [60] | |
USP4 | RIG-I | Deubiquitinates K63-Ub chain | [61,62] | |
USP47 | RIG-I | Deubiquitinates K63-Ub chain | [62] | |
TLR | USP2/USP2a | TRAF6 | Deubiquitinates K63-Ub chain | [70,71] |
USP4 | TAK1, TRAF2, TRAF6 | Deubiquitinates K63-Ub from TAK1 and TRAF6, Deubiquitinates K48-Ub from TRAF6, rescues IκBα from degradation | [72,73,74] | |
USP7 | NF-κB, NEMO, TRAF5 | Deubiquitination | [75,76,77,78,79,80] | |
USP10 | NEMO, TRAF6 | Deubiquitinates K63-Ub from TRAF6, Decrease M1-linked Ub from NEMO | [81,82] | |
USP18 | TAK1, NEMO | Deubiquitinates K63-Ub from TAK1, masks ubiquitin sites of NEMO | [83,113] | |
USP25 | TRAF3 | Deubiquitinates K48-Ub | [57,84,85] | |
USP12 | NF-κB | promotes LPS induced signaling through the dephosphorylation of IκBα. | [86,87] | |
A20 | TRAF6, RIPK1, NEMO | Deubiquitinates K63-Ub from RIPK1, attaches K48-Ub to RIPK1, inhibits ubiquitination of TRAF6, blocks NF-κB activation by binding to NEMO | [88,89,90,91] | |
CYLD | MyD88, RIPK1, TRAF2, NEMO | Deubiquitinates K63-Ub from MyD88, RIPK1, TRAF2 and linear-Ub from NEMO | [43,92,93] | |
MYSM1 | TRAF3, TRAF6 | Deubiquitinates K63-Ub | [94] | |
NLR | A20 | RIPK2, RIPK3 | Deubiquitinates RIPK2 | [107,108] |
BRCC3 | NLRP3 | Deubiquitinates K63-Ub | [99,100] | |
USP7 | NF-κB-p65, NLRP3 | Deubiquitinates K48-Ub from NF-κB-p65, regulates NLRP3 directly or indirectly | [21,79] | |
USP47 | NLRP3 | Regulates NLRP3 directly or indirectly | [109] |
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Rasaei, R.; Sarodaya, N.; Kim, K.-S.; Ramakrishna, S.; Hong, S.-H. Importance of Deubiquitination in Macrophage-Mediated Viral Response and Inflammation. Int. J. Mol. Sci. 2020, 21, 8090. https://doi.org/10.3390/ijms21218090
Rasaei R, Sarodaya N, Kim K-S, Ramakrishna S, Hong S-H. Importance of Deubiquitination in Macrophage-Mediated Viral Response and Inflammation. International Journal of Molecular Sciences. 2020; 21(21):8090. https://doi.org/10.3390/ijms21218090
Chicago/Turabian StyleRasaei, Roya, Neha Sarodaya, Kye-Seong Kim, Suresh Ramakrishna, and Seok-Ho Hong. 2020. "Importance of Deubiquitination in Macrophage-Mediated Viral Response and Inflammation" International Journal of Molecular Sciences 21, no. 21: 8090. https://doi.org/10.3390/ijms21218090