Regulation of immune responses by E3 ubiquitin ligase Cbl-b

Malaria infection induces complex and diverse immune responses. To elucidate the mechanisms underlying host–parasite interaction, we performed a genetic screen during early (24 h) Plasmodium yoelii infection in mice and identified a large number of interacting host and parasite genes/loci after transspecies expression quantitative trait locus (Ts-eQTL) analysis. We next investigated a host E3 ubiquitin ligase gene (March1) that was clustered with interferon (IFN)-stimulated genes (ISGs) based on the similarity of the genome-wide pattern of logarithm of the odds (LOD) scores (GPLS). March1 inhibits MAVS/STING/TRIF-induced type I IFN (IFN-I) signaling in vitro and in vivo. However, in malaria-infected hosts, deficiency of March1 reduces IFN-I production by activating inhibitors such as SOCS1, USP18, and TRIM24 and by altering immune cell populations. March1 deficiency increases CD86+DC (dendritic cell) populations and levels of IFN-γ and interleukin 10 (IL-10) at day 4 post infection, leading to improved host survival. T cell depletion reduces IFN-γ level and reverse the protective effects of March1 deficiency, which can also be achieved by antibody neutralization of IFN-γ. This study reveals functions of MARCH1 (membrane-associated ring-CH–type finger 1) in innate immune responses and provides potential avenues for activating antimalaria immunity and enhancing vaccine efficacy.

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Overexpression of OsPUB41, a Rice E3 ubiquitin ligase induced by cell wall degrading enzymes, enhances immune responses in Rice and Arabidopsis

BMC Plant Biology ◽

10.1186/s12870-019-2079-1 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Neha Rajendra Kachewar ◽

Vishal Gupta ◽

Ashish Ranjan ◽

Hitendra Kumar Patel ◽

Ramesh V. Sonti

Keyword(s):

Cell Wall ◽

Immune Responses ◽

Ubiquitin Ligase ◽

Ectopic Expression ◽

E3 Ubiquitin Ligase ◽

Defense Responses ◽

Cell Wall Degrading Enzymes ◽

Degrading Enzymes ◽

Transient Overexpression ◽

Molecular Patterns

Abstract Background Cell wall degrading enzymes (CWDEs) induce plant immune responses and E3 ubiquitin ligases are known to play important roles in regulating plant defenses. Expression of the rice E3 ubiquitin ligase, OsPUB41, is enhanced upon treatment of leaves with Xanthomonas oryzae pv. oryzae (Xoo) secreted CWDEs such as Cellulase and Lipase/Esterase. However, it is not reported to have a role in elicitation of immune responses. Results Expression of the rice E3 ubiquitin ligase, OsPUB41, is induced when rice leaves are treated with either CWDEs, pathogen associated molecular patterns (PAMPs), damage associated molecular patterns (DAMPs) or pathogens. Overexpression of OsPUB41 leads to induction of callose deposition, enhanced tolerance to Xoo and Rhizoctonia solani infection in rice and Arabidopsis respectively. In rice, transient overexpression of OsPUB41 leads to enhanced expression of PR genes and SA as well as JA biosynthetic and response genes. However, in Arabidopsis, ectopic expression of OsPUB41 results in upregulation of only JA biosynthetic and response genes. Transient overexpression of either of the two biochemically inactive mutants (OsPUB41C40A and OsPUB41V51R) of OsPUB41 in rice and stable transgenics in Arabidopsis ectopically expressing OsPUB41C40A failed to elicit immune responses. This indicates that the E3 ligase activity of OsPUB41 protein is essential for induction of plant defense responses. Conclusion The results presented here suggest that OsPUB41 is possibly involved in elicitation of CWDE triggered immune responses in rice.

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Characterization of E3 ubiquitin ligase neuregulin receptor degradation protein-1 (Nrdp1) in the large yellow croaker (Larimichthys crocea) and its immune responses to Cryptocaryon irritans

Gene ◽

10.1016/j.gene.2014.11.024 ◽

2015 ◽

Vol 556 (2) ◽

pp. 98-105 ◽

Cited By ~ 15

Author(s):

Dong Ling Zhang ◽

Fang Han ◽

Da Hui Yu ◽

Shi Jun Xiao ◽

Ming Yun Li ◽

...

Keyword(s):

Immune Responses ◽

Ubiquitin Ligase ◽

E3 Ubiquitin Ligase ◽

Large Yellow Croaker ◽

Larimichthys Crocea ◽

Cryptocaryon Irritans

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E3 ubiquitin ligase RNF170 inhibits innate immune responses by targeting and degrading TLR3 in murine cells

Cellular and Molecular Immunology ◽

10.1038/s41423-019-0236-y ◽

2019 ◽

Vol 17 (8) ◽

pp. 865-874 ◽

Cited By ~ 5

Author(s):

Xiaoqi Song ◽

Shuo Liu ◽

Wendie Wang ◽

Zhongfei Ma ◽

Xuetao Cao ◽

...

Keyword(s):

Immune Responses ◽

Ubiquitin Ligase ◽

E3 Ubiquitin Ligase ◽

Innate Immune ◽

Innate Immune Responses

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E3 Ubiquitin Ligase Tripartite Motif 38 Negatively Regulates TLR-Mediated Immune Responses by Proteasomal Degradation of TNF Receptor-Associated Factor 6 in Macrophages

The Journal of Immunology ◽

10.4049/jimmunol.1103255 ◽

2012 ◽

Vol 188 (6) ◽

pp. 2567-2574 ◽

Cited By ~ 79

Author(s):

Wei Zhao ◽

Lijuan Wang ◽

Meng Zhang ◽

Chao Yuan ◽

Chengjiang Gao

Keyword(s):

Immune Responses ◽

Ubiquitin Ligase ◽

E3 Ubiquitin Ligase ◽

Proteasomal Degradation ◽

Tnf Receptor ◽

Associated Factor ◽

Tripartite Motif

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AB0040 Effects of CC-220, A CRL4 Cereblon E3 Ubiquitin Ligase Modulator, on Immune Responses

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2015-eular.3487 ◽

2015 ◽

Vol 74 (Suppl 2) ◽

pp. 903.2-903

Author(s):

Y. Ye ◽

P. Schafer ◽

M. Thomas ◽

D. Weiss ◽

A. Gaudy ◽

...

Keyword(s):

Immune Responses ◽

Ubiquitin Ligase ◽

E3 Ubiquitin Ligase

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PUB4, a CERK1-Interacting Ubiquitin Ligase, Positively Regulates MAMP-Triggered Immunity in Arabidopsis

Plant and Cell Physiology ◽

10.1093/pcp/pcz151 ◽

2019 ◽

Vol 60 (11) ◽

pp. 2573-2583 ◽

Cited By ~ 6

Author(s):

Yoshitake Desaki ◽

Shohei Takahashi ◽

Kenta Sato ◽

Kanako Maeda ◽

Saki Matsui ◽

...

Keyword(s):

Immune Responses ◽

Ubiquitin Ligase ◽

Induced Defense ◽

E3 Ubiquitin Ligase ◽

Reactive Oxygen Species Generation ◽

Defense Responses ◽

Knockout Mutant ◽

Double Knockout ◽

Defense Gene Expression ◽

Callose Deposition

Abstract Lysin motif (LysM) receptor-like kinase CERK1 is a co-receptor essential for plant immune responses against carbohydrate microbe-associated molecular patterns (MAMPs). Concerning the immediate downstream signaling components of CERK1, receptor-like cytoplasmic kinases such as PBL27 and other RLCK VII members have been reported to regulate immune responses positively. In this study, we report that a novel CERK1-interacting E3 ubiquitin ligase, PUB4, is also involved in the regulation of MAMP-triggered immune responses. Knockout of PUB4 resulted in the alteration of chitin-induced defense responses, indicating that PUB4 positively regulates reactive oxygen species generation and callose deposition but negatively regulates MAPK activation and defense gene expression. On the other hand, detailed analyses of a double knockout mutant of pub4 and sid2, a mutant of salicylic acid (SA) synthesis pathway, showed that the contradictory phenotype of the pub4 mutant was actually caused by abnormal accumulation of SA in this mutant and that PUB4 is a positive regulator of immune responses. The present and recent findings on the role of PUB4 indicate that PUB4 is a unique E3 ubiquitin ligase involved in the regulation of both plant immunity and growth/development.

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