Regulation of Cellular Antiviral Signaling by Modifications of Ubiquitin and Ubiquitin-like Molecules

Kang Li; Bo Zhong

doi:10.4110/in.2018.18.e4

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Li and Zhong: Regulation of Cellular Antiviral Signaling by Modifications of Ubiquitin and Ubiquitin-like Molecules

Review Article

Immune Netw 2018;18(1):e4.

Published online: 4 February 2018

DOI: https://doi.org/10.4110/in.2018.18.e4

Regulation of Cellular Antiviral Signaling by Modifications of Ubiquitin and Ubiquitin-like Molecules

Kang Li¹, Bo Zhong^1,^2,^*

¹Department of Immunology, Medical Research Institute, School of Medicine, Wuhan University, Wuhan 430071, China

²Department of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China

^*Correspondence to Bo Zhong Medical Research Institute, School of Medicine, Wuhan University, 115 Donghu Road, Wuhan 430071, China. E-mail: zhongbo@whu.edu.cn

Conflict of Interest The authors declare no potential conflicts of interest.

Received 2 October 2017 Revised 19 December 2017 Accepted 21 December 2017

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The initiation of cellular antiviral signaling depends on host pattern-recognition receptors (PRRs)-mediated recognition of viral nucleic acids that are known as classical pathogen-associated molecular patterns (PAMPs). PRRs recruit adaptor proteins and kinases to activate transcription factors and epigenetic modifiers to regulate transcription of hundreds of genes, the products of which collaborate to elicit antiviral responses. In addition, PRRs-triggered signaling induces activation of various inflammasomes which leads to the release of IL-1β and inflammation. Recent studies have demonstrated that PRRs-triggered signaling is critically regulated by ubiquitin and ubiquitin-like molecules. In this review, we first summarize an updated understanding of cellular antiviral signaling and virus-induced activation of inflammasome and then focus on the regulation of key components by ubiquitin and ubiquitin-like molecules.

Keywords: Innate immune responses, Signal transduction, Regulation, Ubiquitin, SUMO, NEDD8, ISG15

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Figure 1.

Virus-triggered PRRs-mediated signaling pathways leading to type I IFN and IL-1β induction.

Figure 2.

The C terminal conserved amino acids of ubiquitin and ubiquitin-like molecules.

Table 1.

Ubiquitin and ubiquitin-like modifications in virus-triggered PRRs-mediated signaling pathways

Target molecules	E3 ligases-mediated ubiquitination	Modification sites	References
PRRs
RIG-I	RNF122 (K48 linkage)	Lys115, Lys 146	Wang et al. (56)
	CHIP (K48 linkage)	ND	Zhao et al. (136)
	CypA-TRIM25 (K63 linkage)	Lys172	Liu et al. (50)
	p97-RNF125 (K48 linkage)	Lys181	Gack et al. (51) Hao et al. (55)
	TRIM40 (K27 and K48 linkage)	ND	Zhao et al. (59)
	Ube2D3, Ube2N (K63 linkage)	Lys48, Lys96, Lys172	Shi et al. (52)
	MUL1 (SUMOylation)	ND	Doiron et al. (105)
	USP15 (K63 linkage)	–	Zhang et al. (60)
	UbcH8 (ISGylation)	ND	Arimoto et al. (118)
	TRIM38 (SUMOylation)	Lys96, Lys888	Hu et al. (106)
	SENP2	–	–
MDA5	TRIM65 (K63 linkage)	Lys743	Lang et al. (67)
	TRIM40 (K27 and K48 linkage)	Lys23, Lys43, Lys68	Zhao et al. (59)
	PIAS2β (SUMOylation)	ND	Fu et al. (104)
	TRIM38 (SUMOylation)	Lys43, Lys865	Hu et al. (106)
cGAS	RNF185 (K27 linkage)	ND	Wang et al. (68)
	TRIM38 (SUMOylation)	Lys83, Lys231, Lys479	Hu et al. (107)
	SENP2	–	–
	SENP7	Lys335, Lys372, Lys382	Cui et al. (108)
	USP14 (K48 linkage)	Lys414	Chen et al. (69)
NLRP3	FBXL12 (K48 linkage)	Lys689	Han et al. (71)
	MARCH7 (K48 linkage)	ND	Yan et al. (72)
AIM2, IFI16	ND	–	–
Adaptor proteins
TRIF	TRIM38 (K48 linkage)	Lys228	Xue et al. (73)
			Hu et al. (74)
	WWP2 (K48 linkage)	ND	Yang et al. (75)
	TRIM32 (ubiquitin-independent)	–	Yang et al. (76)
MyD88	CYLD (K63 linkage)	Lys231	Lee et al. (77)
	Smurf1/2 (K48 linkage)	Lys231, Lys262	Naiki et al. (78)
			Strickson et al. (79)
	Pellino (K48 linkage)	ND	Ji et al. (80)
	ND (NEDDylation)	ND	Yan et al. (131)
VISA	Tetherin-MARCH8 (K48 linkage)	Lys7	Jin et al. (82)
	TRIM31 (K63 linkage)	Lys10, Lys311, Lys461	Liu et al. (24)
	IRTKS-PCBP2 (SUMOylation)	–	Xia et al. (21)
MITA	TRIM29 (K48 linkage)	ND	Xing et al. (83)
	MUL1 (K63 linkage)	Lys224	Ni et al. (84)
	TRIM30α (K48 linkage)	Lys275	Wang et al. (85)
	AMFR (K27 linkage)	–	Wang et al. (25)
	USP21 (K27/63 linkage)	–	Chen et al. (88)
	USP18-USP20 (K48 linkage)	–	Zhang et al. (86)
	USP13 (K27 linkage)	–	Sun et al. (87)
	TRIM38 (SUMOylation)	Lys338	Hu et al. (107)
ASC	TRAF3 (K63 linkage)	Lys174	Guan et al. (95)
TRAF3, TRAF6	ERα (K48 linkage)	ND	Wang et al. (90)
	cIAP1/2 (K63 and K48 linkage)	–	Mao et al. (89)
	USP25 (K48 linkage)	–	Lin et al. (93)
	MYSM1 (K63 linkage)	–	Panda et al. (94)
	HSCARG-OTUB1 (K48 linkage)	–	Peng et al. (91)
Kinases and transcription factors
TBK1	MIB2 (K63 linkage)	ND	Ye et al. (137)
	RNF128 (K63 linkage)	Lys30, Lys401	Song et al. (98)
	USP1–UAF1 (K48 linkage)	ND	Yu et al. (138)
	DYRK2-DTX4 (K48 linkage)	Lys670	Cui et al. (139)
			An et al. (96)
	ND (SUMOylation)	Lys694	Saul et al. (140)
IRF3	c-Cbl (K48 linkage)	ND	Zhao et al. (99)
	LUBAC (linear)	Lys193, Lys313	Chattopadhyay et al. (100)
	ND (SUMOylation)	Lys152	Kubota et al. (110)
	PIAS1 (SUMOylation)	ND	Li et al. (112)
	SENP2	Lys70, Lys87	Yang et al. (22)
	HERC5 (ISGylation)	Lys193, Lys360, Lys366	Lu et al. (119)
			Shi et al. (120)
IRF7	TRIM28 (SUMOylation)	Lys444, Lys446	Liang et al. (111)
	ND (SUMOylation)	Lys406	Kubota et al. (110)
	TRAF6 (K63 linkage)	Lys44, Lys446, Lys452	Ning et al. (101)
Pro-IL-1β	A20 (K63 linkage, unanchored)	Lys133	Duong et al. (141)

ND, not determined.

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