PMID- 34416243
OWN - NLM
STAT- MEDLINE
DCOM- 20210930
LR  - 20210930
IS  - 1872-7786 (Electronic)
IS  - 0009-2797 (Linking)
VI  - 348
DP  - 2021 Oct 1
TI  - RNF31 mediated ubiquitination of A20 aggravates inflammation and hepatocyte 
      apoptosis through the TLR4/MyD88/NF-kappaB signaling pathway.
PG  - 109623
LID - S0009-2797(21)00261-1 [pii]
LID - 10.1016/j.cbi.2021.109623 [doi]
AB  - Inflammatory cytokine storm is one of the main pathogenesis of acute liver 
      injury, and accumulating evidence suggests that the E3 ubiquitin ligase ring 
      finger protein 31 (RNF31) plays an important regulatory role in the activation of 
      inflammatory pathways. We found that RNF31 expression was up-regulated in 
      lipopolysaccharide (LPS)-treated HL-7702 cells. Western blotting results showed 
      decreased expression of RNF31 and total ubiquitinated proteins after transfection 
      of si-RNF31. The results of MTT assay indicated that cell viability was enhanced. 
      Flow cytometry analysis showed that cell apoptosis and ROS content was decreased, 
      and ELISA assay results exhibited that the inflammatory factors secretion was 
      reduced. Interestingly, A20 protein expression was inhibited as RNF31 expression 
      was upregulated. On this basis, we performed co-immunoprecipitation assays and 
      found that RNF31 could interact with A20. Actinomycin tracing and proteasome 
      inhibition experiments showed that RNF31 degrades A20 through the proteasome 
      pathway. Furthermore, overexpression of A20 enhanced cell viability, reduced 
      apoptosis, and inhibited ROS generation and inflammatory factor secretion. 
      Mechanistic studies revealed that RNF31 was able to degrade A20, which affected 
      the inflammatory response and hepatocyte apoptosis mediated by the toll like 
      receptor 4 (TLR4)/myeloid differentiation factor88 (MyD88)/nuclear transcription 
      factor-kappaB (NF-kappaB) signaling pathway. Moreover, knockdown of RNF31 attenuated the 
      inflammatory response induced by d-Gal/LPS in mice with acute liver injury. In 
      conclusion, RNF31 degrades A20 by ubiquitination and activates the 
      TLR4/MyD88/NF-kappaB signaling pathway to aggravate acute liver injury.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Li, Song
AU  - Li S
AD  - Department of laboratory medicine, Zhumadian Central Hospital, Zhumadian, 463000, 
      Henan, China. Electronic address: songlihn@163.com.
FAU - Zheng, Ximing
AU  - Zheng X
AD  - Department of laboratory medicine, Zhumadian Central Hospital, Zhumadian, 463000, 
      Henan, China.
FAU - Hu, Yingchao
AU  - Hu Y
AD  - Department of laboratory medicine, Zhumadian Central Hospital, Zhumadian, 463000, 
      Henan, China.
FAU - You, Kun
AU  - You K
AD  - Department of Hepatobiliary Surgery, First Affiliated Hospital of Xinxiang 
      Medical University, Weihui, 453100, Henan, China.
FAU - Wang, Junda
AU  - Wang J
AD  - Department of Hepatobiliary Surgery, First Affiliated Hospital of Xinxiang 
      Medical University, Weihui, 453100, Henan, China.
LA  - eng
PT  - Journal Article
DEP - 20210817
PL  - Ireland
TA  - Chem Biol Interact
JT  - Chemico-biological interactions
JID - 0227276
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (NF-kappa B)
RN  - 0 (Toll-Like Receptor 4)
RN  - EC 2.3.2.27 (RNF31 protein, human)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 3.4.19.12 (TNFAIP3 protein, human)
RN  - EC 3.4.19.12 (Tumor Necrosis Factor alpha-Induced Protein 3)
SB  - IM
MH  - *Apoptosis
MH  - Cell Line
MH  - Hepatocytes/*pathology
MH  - Humans
MH  - Inflammation/metabolism/pathology
MH  - Myeloid Differentiation Factor 88/metabolism
MH  - NF-kappa B/metabolism
MH  - *Signal Transduction
MH  - Toll-Like Receptor 4/metabolism
MH  - Tumor Necrosis Factor alpha-Induced Protein 3/*metabolism
MH  - Ubiquitin-Protein Ligases/*metabolism
MH  - *Ubiquitination
OTO - NOTNLM
OT  - A20 protein
OT  - Inflammation
OT  - Liver injury
OT  - Ring finger protein 31
OT  - The TLR4/MyD88/NF-kappaB signaling pathway
OT  - Ubiquitination
EDAT- 2021/08/21 06:00
MHDA- 2021/10/01 06:00
CRDT- 2021/08/20 20:12
PHST- 2021/06/16 00:00 [received]
PHST- 2021/08/16 00:00 [accepted]
PHST- 2021/08/21 06:00 [pubmed]
PHST- 2021/10/01 06:00 [medline]
PHST- 2021/08/20 20:12 [entrez]
AID - S0009-2797(21)00261-1 [pii]
AID - 10.1016/j.cbi.2021.109623 [doi]
PST - ppublish
SO  - Chem Biol Interact. 2021 Oct 1;348:109623. doi: 10.1016/j.cbi.2021.109623. Epub 
      2021 Aug 17.