ARRDC3

Last update 08 May 2025

Basic Info

Synonyms

ARRDC3, arrestin domain containing 3, Arrestin domain-containing protein 3

+ [3]

Introduction

Adapter protein that plays a role in regulating cell-surface expression of adrenergic receptors and probably also other G protein-coupled receptors (PubMed:20559325, PubMed:21982743, PubMed:23208550). Plays a role in NEDD4-mediated ubiquitination and endocytosis af activated ADRB2 and subsequent ADRB2 degradation (PubMed:20559325, PubMed:23208550). May recruit NEDD4 to ADRB2 (PubMed:20559325). Alternatively, may function as adapter protein that does not play a major role in recruiting NEDD4 to ADRB2, but rather plays a role in a targeting ADRB2 to endosomes (PubMed:23208550).

100 Clinical Results associated with ARRDC3

100 Translational Medicine associated with ARRDC3

0 Patents (Medical) associated with ARRDC3

Literatures (Medical) associated with ARRDC3

01 Jun 2025·Metabolism

Arrestin domain containing 3 promotes alcohol-induced liver steatosis by reducing stearoyl-CoA desaturase-1 ubiquitinated degradation

Article

Author: Liu, Huiling ; Zhong, Zhenwei ; Tang, Ying ; Zhou, Haoxiong ; Pan, Xuemei ; Guo, Yunwei

BACKGROUND AND AIMSAlcoholic liver disease (ALD) is a major cause of chronic liver disease worldwide with no approved therapy. The development of ALD is strongly associated with hepatic lipid accumulation. Arrestin domain containing 3 (ARRDC3), a member of the α-arrestin family, is involved in obesity, inflammation, and cancer. However, its role in ALD remains largely unexplored.METHODSBoth the NIAAA and traditional Lieber-De Carli mouse models of ALD were employed. ARRDC3 expression was evaluated in liver specimens from ALD patients, mouse hepatic tissues, and hepatocytes. Hepatocyte-targeted Arrdc3 knockdown was achieved through intrahepatic delivery of adeno-associated virus 8 (AAV8) carrying shRNA under a hepatocyte-specific promoter. Mass spectrometry analysis, immunofluorescence, co-immunoprecipitation (co-IP) assays, and molecular docking were used to identify the interaction between ARRDC3 and stearoyl-CoA desaturase 1 (SCD1).RESULTSARRDC3 levels were significantly elevated in the livers of both ALD patients and mouse models. Knockdown of Arrdc3 using AAV8 alleviated alcohol-induced liver steatosis in both the NIAAA and traditional Lieber-De Carli mouse models. We demonstrated that ARRDC3 promoted the progression of ALD by inducing lipid accumulation in hepatocytes. Mechanistically, ARRDC3 directly binds to SCD1 and inhibits its ubiquitin-proteasome degradation. Inhibition of SCD1 blocked ARRDC3-induced lipid deposition in hepatocytes. We also observed a correlation between ARRDC3 and SCD1 in liver samples from ALD patients.CONCLUSIONSOur findings reveal that ARRDC3 promotes hepatic steatosis in ALD by reducing the ubiquitin-dependent degradation of SCD1. ARRDC3 may serve as a potential therapeutic target for ALD.

11 Apr 2025·Radiation Research

The Radioprotective Effects of 16, 16 dimethyl Prostaglandin E2 on Survival and Hematopoiesis are Mediated Through Co-Stimulation of the EP3 and EP4 Receptors

Article

Author: Patterson, Andrea M. ; Sampson, Carol H. ; Singh, Pratibha ; Fukuda, Seiji ; Orschell, Christie M. ; Feng, Hailin ; Plett, P. Artur ; Pelus, Louis M. ; Wu, Tong

16, 16 dimethyl-Prostaglandin E2 (dmPGE2) administered prior to lethal irradiation protects against mortality from the hematopoietic acute radiation syndrome (H-ARS). It protects hematopoietic stem (HSC) and progenitor (HPC) cells and accelerates hematopoietic recovery by attenuating mitochondrial compromise, epigenetic downregulation of p53, and inhibition of histone acetylation at the promoters of genes involved in cell cycle, DNA repair and apoptosis. Since PGE2 mediates it effects through 4 conserved G-protein coupled receptors (EP1-4) we utilized highly selective EP receptor agonists to identify the EP receptors mediating radioprotection in H-ARS and evaluated the genes, cellular pathways and biological functions downstream of the EP receptors involved in HSC radioprotection. Radioprotection of mice from lethal radiation exposure was observed for the EP3 agonist sulprostone (65% survival) and the EP4 agonist rivenprost (50% survival), with the combination of EP3 + EP4 agonists providing 100% survival. Misoprostol, a PGE1 analog with similar EP receptor affinities as dmPGE2 also provided >90% survival. The combination of EP3 and EP4 agonists was highly efficacious in accelerating recovery of all peripheral blood cell counts. Analysis of bone marrow HSPC populations from lethally irradiated mice by flow cytometry indicated that the EP3 + EP4 agonist combination trended closest to dmPGE2 in protecting total HSC and HPC, preventing early entry of these cells into cell cycle, and attenuating radiation-induced upregulation of the proapoptotic death receptor Fas, with similar activity also shown by misoprostol. Several genes involved in cell cycle and/or apoptosis control were upregulated (s1pr1, arrdc3, osm) or downregulated (hcar2 and cxcl10) in HSCs by all efficacious agonist treatments. Analysis of gene expression profiles and functional pathway analysis in HSC suggests that the EP4 receptor signals primarily through cAMP/PKA/CREB1, while EP3 signals primarily through a PI3K/Akt pathway initiated through activation of the Ras/Rho GTPases. In the combination setting, EP4 signaling appears dominant. Co-stimulation of EP3 and EP4 gave a stronger z-score for CREB1 activation with EP3 signaling augmenting/enhancing gene expression downstream of EP4 predominantly through CREB1. Comparison of KEGG pathways regulated by dmPGE2 and those regulated by the combination of EP3 + EP4 agonists indicate that both groups' TNF signaling pathways may be key functional components for radioprotection by dmPGE2 in HSC. Differentially expressed genes (DEG) associated with GTPase activity were observed in HSCs from mice treated with both EP3 and EP4 agonists likely contributing to their enhanced radioprotective effect mediated through the PI3K/Akt pathways downstream of both receptors. Some upstream regulators most strongly activated by dmPGE2 in bone marrow stromal cells overlapped with those observed in HSCs, with the most striking similarity being inhibition of p53 activation. In summary, these studies show that signaling through both the EP3 and EP4 PGE receptors recapitulates maximal radioprotection of mice from H-ARS by dmPGE2 via inhibition of cell cycle progression and apoptosis.

01 Apr 2025·Microbiology and Immunology

Analysis of the Functional Role of TIMM29 in the Hepatitis B Virus Life Cycle

Article

Author: Kimura‐Ohba, Shihoko ; Muriungi, Nelly ; Suwanmanee, Yadarat ; Ueda, Keiji ; Abueldahab, Limia ; Wada, Masami ; Ohsaki, Eriko

ABSTRACTHepatitis B virus (HBV) causes chronic hepatitis B, which can progress to liver cirrhosis and hepatocellular carcinoma. HBV has complex interactions with various cell organelles and proteins that ensure effective progeny virus production. We previously reported that a mitochondrial protein, TIMM29, should regulate the HBV life cycle through interactions with the HBV preS1 protein. Here, we established Halo‐TIMM29wt‐, Halo‐TIMM29:∆99–192‐, and Halo‐TIMM29:92–194‐expressing cells using TIMM29‐knockout HB611 (TIMM29KO/HB611) cells, a stably HBV‐producing cell line based on Huh6 cells. We found that HBV antigen expression and replication were downregulated in cells stably expressing full‐length TIMM29, but not in those expressing TIMM29 deletion mutants. On the other hand, in the case of TIMM29‐knockout C4 (TIMM29KO/C4), which is a human NTCP‐expressing HepG2 cell line that is competent for HBV infection and amplification, these phenomena were not reproduced, except in full‐length TIMM29 (Halo‐TIMM29wt)‐expressing cells. Using gene expression microarrays, we identified downregulation of ARRDC3 and BASP1 in TIMM29KO/HB611 and TIMM29KO/C4. It was suggested that TIMM29 localized at the mitochondrial inner membrane served as a signaling hub, orchestrating the activation of ARRDC3 and BASP1 expression to restrict HBV transcription. The expression of TIMM29 mutants in TIMM29KO/HB611 and TIMM29KO/C4 cells suggested that ARRDC3 was dependent on the HBV preS1‐binding region of TIMM29 (amino acids 99–189). In contrast, BASP1 expression varied according to cell type, indicating additional regulatory mechanisms. Thus, this study should significantly advance our understanding of TIMM29‐mediated inhibition of HBV amplification and lead to improvements in antiviral strategies and therapeutic interventions against HBV.

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ARRDC3

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