Multifaceted Roles of the E3 Ubiquitin Ligase RING Finger Protein 115 in Immunity and Diseases

Wang, Meixia; Liuyu, Tianzi; Zhang, Zhidong

doi:10.3389/fimmu.2022.936579

Cited by 6 publications

(1 citation statement)

References 62 publications

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“…RNF115 orchestrates the ubiquitination of specific proteins, influencing related signaling cascades. This modulation impacts viral infections, autoimmunity, cell growth, and tumor development (Wang et al 2022 ). RNF115 has been identified as a regulator in lung adenocarcinoma, where it promotes cellular growth and metabolism while suppressing apoptosis.…”

Section: Discussionmentioning

confidence: 99%

RNF115 aggravates tumor progression through regulation of CDK10 degradation in thyroid carcinoma

Zhu,

Guo,

Dai

et al. 2024

Cell Biol Toxicol

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Background RING Finger Protein 115 (RNF115), a notable E3 ligase, is known to modulate tumorigenesis and metastasis. In our investigation, we endeavor to unravel the putative function and inherent mechanism through which RNF115 influences the evolution of thyroid carcinoma (THCA). Methods We analyzed RNF115 expression in THCA using the Cancer Genome Atlas (TCGA) database. The influence of RNF115 on the progression of THCA was evaluated using both in vitro and in vivo experimental approaches. The protein regulated by RNF115 was identified through bioinformatics analysis, and its biological significance was further explored. Results In both THCA tissues and cells, RNF115 showed elevated expression levels. Enhanced expression of RNF115 fostered cell proliferation, tumor growth, and the exacerbation of epithelial-mesenchymal transition (EMT) in THCA, while also promoting tumor lung metastasis. Bioinformatics analysis identified cyclin-dependent kinase 10 (CDK10) as a downstream target of RNF115, which was found to be ubiquitinated and degraded by RNF115 in THCA cells. Functionally, overexpression of CDK10 was found to counteract the promotion of malignant phenotype in THCA induced by RNF115. From a mechanistic perspective, RNF115 activated the Raf-1 pathway and enhanced cancer cell cycle progression by degrading CDK10 in THCA cells. Conclusion RNF115 triggers cell proliferation, EMT, and tumor metastasis by ubiquitinating and degrading CDK10. The regulation of the Raf-1 pathway and cell cycle progression in THCA may be profoundly influenced by this process.

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Section: Discussionmentioning

confidence: 99%

RNF115 aggravates tumor progression through regulation of CDK10 degradation in thyroid carcinoma

Zhu,

Guo,

Dai

et al. 2024

Cell Biol Toxicol

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RNF115/BCA2 deficiency alleviated acute liver injury in mice by promoting autophagy and inhibiting inflammatory response

Feng,

Ye,

Hai

et al. 2023

Cell Death Dis

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The E3 ubiquitin ligase RING finger protein 115 (RNF115), also known as breast cancer-associated gene 2 (BCA2), has been linked with the growth of some cancers and immune regulation, which is negatively correlated with prognosis. Here, it is demonstrated that the RNF115 deletion can protect mice from acute liver injury (ALI) induced by the treatment of lipopolysaccharide (LPS)/D-galactosamine (D-GalN), as evidenced by decreased levels of alanine aminotransaminase, aspartate transaminase, inflammatory cytokines (e.g., tumor necrosis factor α and interleukin-6), chemokines (e.g., MCP1/CCL2) and inflammatory cell (e.g., monocytes and neutrophils) infiltration. Moreover, it was found that the autophagy activity in Rnf115−/− livers was increased, which resulted in the removal of damaged mitochondria and hepatocyte apoptosis. However, the administration of adeno-associated virus Rnf115 or autophagy inhibitor 3-MA impaired autophagy and aggravated liver injury in Rnf115−/− mice with ALI. Further experiments proved that RNF115 interacts with LC3B, downregulates LC3B protein levels and cell autophagy. Additionally, Rnf115 deletion inhibited M1 type macrophage activation via NF-κB and Jnk signaling pathways. Elimination of macrophages narrowed the difference in liver damage between Rnf115+/+ and Rnf115−/− mice, indicating that macrophages were linked in the ALI induced by LPS/D-GalN. Collectively, for the first time, we have proved that Rnf115 inactivation ameliorated LPS/D-GalN-induced ALI in mice by promoting autophagy and attenuating inflammatory responses. This study provides new evidence for the involvement of autophagy mechanisms in the protection against acute liver injury.

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Disulfiram ameliorates STING/MITA-dependent inflammation and autoimmunity by targeting RNF115

Zhang,

Shi,

et al. 2024

Cell Mol Immunol

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Multifaceted Roles of the E3 Ubiquitin Ligase RING Finger Protein 115 in Immunity and Diseases

Cited by 6 publications

References 62 publications

RNF115 aggravates tumor progression through regulation of CDK10 degradation in thyroid carcinoma

RNF115 aggravates tumor progression through regulation of CDK10 degradation in thyroid carcinoma

RNF115/BCA2 deficiency alleviated acute liver injury in mice by promoting autophagy and inhibiting inflammatory response

Disulfiram ameliorates STING/MITA-dependent inflammation and autoimmunity by targeting RNF115

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