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Last update 08 May 2025

RNF19B

Last update 08 May 2025

Basic Info

Synonyms

E3 ubiquitin-protein ligase RNF19B, FLJ90005, IBR domain-containing protein 3

+ [5]

Introduction

E3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes UBE2L3 and UBE2L6 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates, such as UCKL1 (PubMed:16709802, PubMed:27485036). Involved in the cytolytic activity of natural killer cells and cytotoxic T-cells (PubMed:10438909). Protects against staurosporin-induced cell death (PubMed:27485036).

Drugs associated with RNF19B

BRD-1732

Target

RNF19A x RNF19B

Mechanism

RNF19A inhibitors [+1]

Active Org.

UCSF

Originator Org.

UCSF

Active Indication-

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with RNF19B

100 Translational Medicine associated with RNF19B

0 Patents (Medical) associated with RNF19B

Literatures (Medical) associated with RNF19B

01 Apr 2025·Journal of Biological Chemistry

The ubiquitin ligase NKLAM promotes apoptosis and suppression of cell growth

Article

Author: Willard, Paul A ; Kornbluth, Jacki

Natural Killer Lytic Associated Molecule (NKLAM), also known as RNF19b, is a member of the RING-in between-RING-RING (RBR) E3 ubiquitin ligase family and plays a pivotal role in immune regulation. We identified a critical cysteine residue at position 301 essential for NKLAM's ubiquitin ligase function. Site-directed mutagenesis of this residue to serine or alanine abrogated the ligase activity of NKLAM. Utilizing inducible expression systems in two different cell lines, HEK293 embryonic kidney cells and K562 myeloid leukemia cells, we demonstrated that wild-type (WT) NKLAM, but not the catalytically inactive NKLAM alanine mutant (C301A), inhibited cellular proliferation, as evidenced by reduced cell numbers and decreased metabolic activity. Moreover, NKLAM expression led to a significant decrease in the abundance and stability of the proto-oncogene c-Myc, a key regulator of proliferation. NKLAM facilitated the proteasomal degradation of c-Myc, with a reduction in c-Myc half-life from 27 minutes to 12 minutes and restoration of c-Myc levels upon proteasome inhibition. Notably, prolonged NKLAM expression induced apoptosis, measured by annexin-V staining and caspase activation. Strikingly, the serine mutant, C301S, while lacking ubiquitin ligase activity, induced apoptosis comparable to WT NKLAM, highlighting an alternative pathway for NKLAM-mediated inhibition of cellular homeostasis. Our findings indicate that NKLAM is a cytolytic protein with multifaceted roles in cellular proliferation and apoptosis.

01 Jan 2024·International Archives of Allergy and Immunology

Applying Artificial Intelligence to Identify Common Targets for Treatment of Asthma, Eczema, and Food Allergy

Article

Author: Chen, Michelle ; Mendelsohn, Andrew R ; Rayner, Andre ; Shneyderman, Anastasia ; Pun, Frank W ; Liu, Hei Man

Introduction: Allergic disorders are common diseases marked by the abnormal immune response toward foreign antigens that are not pathogens. Often patients with food allergy also suffer from asthma and eczema. Given the similarities of these diseases and a shortage of effective treatments, developing novel therapeutics against common targets of multiple allergies would offer an efficient and cost-effective treatment for patients. Methods: We employed the artificial intelligence-driven target discovery platform, PandaOmics, to identify common targets for treating asthma, eczema, and food allergy. Thirty-two case-control comparisons were generated from 15, 11, and 6 transcriptomics datasets related to asthma (558 cases, 315 controls), eczema (441 cases, 371 controls), and food allergy (208 cases, 106 controls), respectively, and allocated into three meta-analyses for target identification. Top-100 high-confidence targets and Top-100 novel targets were prioritized by PandaOmics for each allergic disease. Results: Six common high-confidence targets (i.e., IL4R, IL5, JAK1, JAK2, JAK3, and NR3C1) across all three allergic diseases have approved drugs for treating asthma and eczema. Based on the targets’ dysregulated expression profiles and their mechanism of action in allergic diseases, three potential therapeutic targets were proposed. IL5 was selected as a high-confidence target due to its strong involvement in allergies. PTAFR was identified for drug repurposing, while RNF19B was selected as a novel target for therapeutic innovation. Analysis of the dysregulated pathways commonly identified across asthma, eczema, and food allergy revealed the well-characterized disease signature and novel biological processes that may underlie the pathophysiology of allergies. Conclusion: Altogether, our study dissects the shared pathophysiology of allergic disorders and reveals the power of artificial intelligence in the exploration of novel therapeutic targets.

12 Dec 2023·Journal of Biomolecular Structure and Dynamics

Comprehensive analysis and validation reveal potential MYCN regulatory biomarkers associated with neuroblastoma prognosis

Article

Author: Qin, Xiuni ; Chen, Bo

Neuroblastoma (NB) is an embryonic malignant tumor that occurs in the sympathetic nervous system. The treatment results of patients in the high-risk group are poor, and relapse and treatment failure can occur even with multiple combination treatments. The proto-oncogene MYCN is a BHLH Transcription Factor used as an independent prognostic factor for NB. The proportion of MYCN amplification in tumor tissues of high-risk patients reaches 40-50%. Hence, exploring new MYCN target genes is a meaningful approach in developing treatment for high-risk NB patients. The microarray datasets were obtained from Gene Expression Omnibus (GEO), and differentially expressed genes (DEGs) were identified. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and miRPathDB were used for enrichment analysis. STRING and Cytoscape were used to construct a protein-protein interaction (PPI) network and for modular analysis. The miRNet and NetworkAnalyst databases were used to predict and construct gene-miRNA and gene-TFs networks. The R2 database was used for expression, correlation, and prognostic analyses. The diagnostic value of the biomarkers was predicted by ROC analysis, and RT-qPCR was used to validate the identified hub genes. Finally, using specific MYCN siRNA and overexpressing plasmids, the correlation between the identified hub genes and MYCN was investigated. Our results showed that FBXO9, HECW2, MIB2, RNF19B, RNF213, TRIM36, and ZBTB16 are novel biomarkers that affect the prognosis of the NB patients. In addition, FBXO9, RNF19B, and TRIM36 were preliminarily confirmed as potential target genes of MYCN. Overall, FBXO9, HECW2, MIB2, RNF19B, RNF213, TRIM36, and ZBTB16 are expected to become novel biomarkers for the treatment of high-risk NB patients.Communicated by Ramaswamy H. Sarma.

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RNF19B

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