Table 1.
The multiple roles of deubiquitylating enzymes (DUBs) in pattern-recognition receptor (PRR) signaling.
| DUBs | Substrate | Positive regulation | Negative regulation | References |
|---|---|---|---|---|
| USP13 | STING, STAT1 | Stabilizing STAT1 expression | Removing K27/33-linked polyubiquitin chains from STING | Yeh et al., 2013; Sun et al., 2017 |
| USP14 | RIG-I, CGAS | Recruited by TRIM14 to stabilize CGAS and promote IFNs production. | Removing K63-linked polyubiquitin chains from RIG-I | Chen et al., 2016; Li et al., 2019a |
| USP15 | RIG-I, TBK1 | Stabilizing the expression of TRIM25 | Removing K63-linked polyubiquitin chains from RIG-I; Recruited by UBE2S to deubiquitinating TBK1 | Pauli et al., 2014; Zhang et al., 2015 |
| USP18 | TAK1, NEMO, STING, MAVS, IFNAR2 | Acting as a Scaffold protein to recruit USP20 and TRIM31, stabilizing STING and MAVS, respectively. | Interrupting the interaction between IFNAR2 and JAK1; removing K63-linked polyubiquitin chains from TAK1 and NEMO | Malakhova et al., 2006; Liu et al., 2013; Yang et al., 2015; Zhang et al., 2016; Hou et al., 2021 |
| USP27X | RIG-I, CGAS | Removing K48-linked polyubiquitin chains from CGAS | Removing K63-linked polyubiquitin chains from RIG-I | Guo et al., 2019; Tao et al., 2020 |
| OTUD4 | Myd88, TRAF6, MAVS | Removing K48-linked polyubiquitin chains from MAVS | Deubiquitinating K63-linked polyubiquitin chain from TRAF6 and Myd88 | Zhao et al., 2018; Liuyu et al., 2019; Liu et al., 2020 |
| OTUD5 (DUBA) | TRAF3, STING | Removing K48-linked polyubiquitin chain on STING | Removing the K63-linked polyubiquitin chain on TRAF3 | Kayagaki et al., 2007; Guo et al., 2021b |
| OTUB1 | RIG-I, TRAF3, TRAF6 | Deubiquitinating K48-linked ubiquitin chain or forming a complex with UBCH5c to activate RIG-I | Removing K63-linked polyubiquitin chains on TRAF3/TARF6. | Li et al., 2010; Jahan et al., 2020 |
| CYLD | TRAF2, TRAF6, NEMO, RIP1, TBK1, STING, RIG-I | Removing K63-linked polyubiquitin chains on RIG-I and TRAF2/6; Removing linear ubiquitin chain on NEMO; Inhibiting the enzymatic activity of TBK1 | Removing K48-linked polyubiquitin chains on STING. | Yoshida et al., 2005; Zhang et al., 2006; Friedman et al., 2008; Genin et al., 2015; Lork et al., 2018; Zhang et al., 2018 |