RNF5

Last update 08 May 2025

Basic Info

Synonyms

E3 ubiquitin-protein ligase RNF5, G16, HsRma1

+ [6]

Introduction

Membrane-bound E3 ubiquitin-protein ligase that mediates ubiquitination of target proteins (PubMed:11329381, PubMed:12861019, PubMed:16176924, PubMed:19269966, PubMed:19285439). May function together with E2 ubiquitin-conjugating enzymes UBE2D1/UBCH5A and UBE2D2/UBC4 (PubMed:11329381). Mediates ubiquitination of PXN/paxillin,thereby regulating cell motility and localization of PXN/paxillin (PubMed:12861019). Catalyzes ubiquitination of Salmonella type III secreted protein sopA (PubMed:16176924). Mediates the 'Lys-63'-linked polyubiquitination of JKAMP thereby regulating JKAMP function by decreasing its association with components of the proteasome and ERAD; the ubiquitination appears to involve E2 ubiquitin-conjugating enzyme UBE2N (PubMed:19269966). Mediates the 'Lys-48'-linked polyubiquitination of STING1 at 'Lys-150' leading to its proteasomal degradation; the ubiquitination occurs in mitochondria after viral transfection and regulates antiviral responses (PubMed:19285439). Catalyzes ubiquitination and subsequent degradation of ATG4B, thereby inhibiting autophagy (PubMed:23093945).

100 Clinical Results associated with RNF5

100 Translational Medicine associated with RNF5

0 Patents (Medical) associated with RNF5

106

Literatures (Medical) associated with RNF5

06 Mar 2025·Blood

Lasalocid A selectively induces the degradation of MYD88 in lymphomas harboring the MYD88 L265P mutation

Article

Author: Young, Ken H. ; Cao, Ya ; Wang, Ruirui ; Wang, Junhao ; Li, Yong ; Chai, Dafei ; Li, Wei ; Yu, Xinfang ; Xie, Xiaohui

AbstractMyeloid differentiation primary response protein 88 (MYD88) is a key adaptor molecule in the signaling pathways of toll-like receptor and interleukin-1 receptor. A somatic mutation resulting in a leucine-to-proline change at position 265 of the MYD88 protein (MYD88 L265P) is one of the most prevalent oncogenic mutations found in patients with hematological malignancies. In this study, we used high-throughput screening to identify lasalocid A as a potent small molecule that selectively inhibited the viability of lymphoma cells expressing MYD88 L265P and the associated activation of NF-κB. Further investigations using CRISPR-CRISPR–associated protein 9 genetic screening, proteomics, and biochemical assays revealed that lasalocid A directly binds to the MYD88 L265P protein, enhancing its interaction with the ubiquitin ligase RNF5. This interaction promotes MYD88 degradation through the ubiquitin-dependent proteasomal pathway, specifically in lymphomas with the MYD88 L265P mutation. Lasalocid A exhibited strong antitumor efficacy in xenograft mouse models, induced disease remission in ibrutinib-resistant lymphomas, and showed synergistic activity with the B-cell lymphoma 2 inhibitor venetoclax. This study highlights the potential of inducing MYD88 L265P degradation using small molecules, offering promising strategies for treating lymphomas that harbor the MYD88 L265P mutation.

01 Feb 2025·Cancer Letters

RNF5 exacerbates steatotic HCC by enhancing fatty acid oxidation via the improvement of CPT1A stability

Article

Author: Yuan, Yufeng ; Xu, Kequan ; Zhang, Minghe ; Ju, Yi ; Pan, Xiaoyu ; Wu, Tiangen ; Chen, Xi ; Ma, Weijie ; He, Wenzhi ; Li, Xiaomian ; Li, Jinghua ; Dai, Caixia ; Ren, Hui ; Zhang, Yang-Wen-Qing ; Xia, Peng

Non-alcoholic fatty liver disease (NAFLD) is expected to become the leading risk factor for liver cancer, surpassing viral hepatitis. Unlike viral hepatitis-related hepatocellular carcinoma (HCC), the role of excessive nutrient supply in steatotic HCC is not well understood, hindering effective prevention and treatment strategies. Therefore, it is crucial to identify key molecules in the pathogenesis of steatotic HCC, investigate changes in metabolic reprogramming due to excessive fatty acid (FA) supply, understand its molecular mechanisms, and find potential therapeutic targets. Trans-species transcriptome analysis identified Ring Finger Protein 5 (RNF5) as a critical regulator of steatotic HCC. RNF5 upregulation is associated with poor prognosis in steatotic HCC compared to canonical HCC. In vitro and in vivo studies showed that RNF5 exacerbates HCC in the presence of additional FA supply. Lipidomics and transcriptome analyses revealed that RNF5 significantly increases carnitine palmitoyltransferase 1A (CPT1A) mRNA levels and is positively correlated with fatty acid oxidation (FAO). Protein interaction analysis demonstrated that RNF5 promotes K63-type ubiquitination of insulin-like growth factor-2 mRNA-binding protein 1 (IGF2BP1), enhancing CPT1A mRNA stabilization through m6A modification. Additionally, peroxisome proliferator-activated receptor gamma (PPARγ) was found to activate RNF5 expression specifically in HCC cells. Mechanistically, excessive exogenous FAs reorganize FA metabolism in HCC cells, worsening steatotic HCC via the PPARγ-RNF5-IGF2BP1-CPT1A axis. This study highlights a distinct FA metabolism pattern in steatotic HCC, providing valuable insights for potential therapeutic targets.

31 Jan 2025·Journal of Virology

Swine RNF5 positively regulates the antiviral activity of IFITM1 by mediating the degradation of ABHD16A

Article

Author: Shi, Xuemeng ; Ding, Yunyun ; Liu, Mingyang ; Xu, Jun ; Shen, Lingyi ; Wen, Xin ; Liu, Wei ; Wang, Jingyi ; Mao, Lin ; Chen, Shuaiwu ; Yu, Li

ABSTRACTInterferon-inducible transmembrane (IFITM) proteins are broad-spectrum antiviral factors that confer cellular resistance to virus invasion. α/β-Hydrolase domain-containing 16A (ABHD16A) has recently been identified as a novel depalmitoylase that can inhibit the antiviral activity of IFITM proteins by catalyzing the depalmitoyl reaction; this pattern may be crucial for the host to avoid damage caused by excessive immune response. However, it remains largely elusive about how host cells regulate the activity of ABHD16A. In the present study, we performed the AlphaFold2-based protein-protein interaction prediction and identified swine E3 ubiquitin ligase ring finger protein 5 (sRNF5) as a sABHD16A-interacting protein and negatively regulated the stability of sABHD16A. Using immunofluorescence and co-immunoprecipitation techniques, we uncovered that sRNF5 targeted sABHD16A for ubiquitination and degradation via the proteasomal pathway at residues K3 and K452. Furthermore, sABHD16A catalyzed the depalmitoylation of sIFITM1, which obstructed the antiviral function of sIFITM1, while sRNF5 caused ubiquitination of sABHD16A, which attenuated the depalmitoylation effect on sIFITM1, and consequently restored the antiviral activity of sIFITM1. Collectively, our findings demonstrate for the first time that sRNF5 positively regulates the antiviral function of sIFITM1 by mediating the degradation of sABHD16A, which expands the biological functions of RNF5 and ABHD16A in immune regulation. Moreover, our work highlights the well-designed interplay between RNF5, ABHD16A, and IFITM, which balances antiviral immune responses to avoid the disorders induced by excessive immune response.IMPORTANCEInterferon and interferon-stimulated genes play significant and protective roles in the host’s defense against viral infection. IFITM family proteins, which can be strongly induced by interferon, have been identified as the first line of defense to prevent invasion of various viruses. Further analysis reveals the antiviral activity of IFITMs depends on palmitoylation/depalmitoylation. Recently, we reported that ABHD16A, as the first depalmitoylase of IFITMs, negatively regulated the antiviral activity of IFITMs. However, these raise crucial questions: how ABHD16A is regulated and remained in a balanced manner? Here, we show that swine RNF5 attenuates the negative regulation of sIFITM1 against virus invasion by modifying sABHD16A through ubiquitination and guiding sABHD16A for degradation. Thus, sRNF5-sABHD16A interplay plays an indispensable role in regulating immune response and avoiding the disorders induced by elevated interferon levels. Overall, our findings extend the upstream subtle regulatory molecular mechanism of IFITMs and provide potential targets for viral disease therapy.

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RNF5

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