Request Demo

Last update 08 May 2025

TRIM4

Last update 08 May 2025

Basic Info

Synonyms

E3 ubiquitin-protein ligase TRIM4, RING finger protein 87, RING-type E3 ubiquitin transferase TRIM4

+ [4]

Introduction

E3 ubiquitin-protein ligase. Mediates 'Lys-63'-linked polyubiquitination of the innate immune receptor RIGI, this linkage doesn't lead to proteasomal degradation but seems to enhance IFN induction.

Drugs associated with TRIM4

PJ2-02

Target

TRIM4

Mechanism

TRIM4 modulators

Active Org.

StemRIM, Inc.

Originator Org.

StemRIM, Inc.

Active Indication

Soft Tissue Injuries

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with TRIM4

100 Translational Medicine associated with TRIM4

0 Patents (Medical) associated with TRIM4

Literatures (Medical) associated with TRIM4

01 Feb 2025·Frontiers of Medicine

TRIM4 modulates the ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitor in ovarian cancer

Article

Author: Wang, Yiwei ; Che, Xiaoxia ; Feng, Weiwei ; Zhu, Chongying ; Shen, Yuhong ; Shen, Lifei ; Ruan, Yiyin ; Guan, Xin ; Zhou, Tianyu ; Liu, Hua

Ovarian cancer is the most lethal malignancy affecting the female reproductive system. Pharmacological inhibitors targeting CDK4/6 have demonstrated promising efficacy across various cancer types. However, their clinical benefits in ovarian cancer patients fall short of expectations, with only a subset of patients experiencing these advantageous effects. This study aims to provide further clinical and biological evidence for antineoplastic effects of a CDK4/6 inhibitor (TQB4616) in ovarian cancer and explore underlying mechanisms involved. Patient-derived ovarian cancer organoid models were established to evaluate the effectiveness of TQB3616. Potential key genes related to TQB3616 sensitivity were identified through RNA-seq analysis, and TRIM4 was selected as a candidate gene for further investigation. Subsequently, co-immunoprecipitation and GST pull-down assays confirmed that TRIM4 binds to hnRNPDL and promotes its ubiquitination through RING and B-box domains. RIP assay demonstrated that hnRNPDL binded to CDKN2C isoform 2 and suppressed its expression by alternative splicing. Finally, in vivo studies confirmed that the addition of siTRIM4 significantly improved the effectiveness of TQB3616. Overall, our findings suggest that TRIM4 modulates ubiquitin-mediated degradation of hnRNPDL and weakens sensitivity to CDK4/6 inhibitors in ovarian cancer treatment. TRIM4 may serve as a valuable biomarker for predicting sensitivity to CDK4/6 inhibitors in ovarian cancer.

21 Oct 2024·Theranostics

TRIM4 enhances small-molecule-induced neddylated-degradation of CORO1A for triple negative breast cancer therapy

Article

Author: Chen, Yi-Li ; Jin, Yi ; Shen, Yi-Wen ; Liu, Xiao-Xia ; Zhang, Wei-Dong ; Luan, Xin ; Gu, Wen-Jie ; Zhan, Zha-Jun ; Lu, Dong ; Chen, Hong-Zhuan ; Zhang, Li-Jun ; Lin, Jiayi ; Gong, Yi-Ting ; Jin, Jin-Mei

Background: As a critical member of the Coronin family, Coronin 1A (CORO1A) plays a crucial role in the progression of triple-negative breast cancer (TNBC). However, CORO1A is typically considered "undruggable" due to its smooth surface and complex protein-protein interactions (PPIs). Molecular glues have emerged as one of the most effective strategies to rapidly degrade such "undruggable" targets. Neddylation, an emerging approach, has shown promise in targeting pathogenic proteins for degradation through the NEDD8 pathway, making the degradation of CORO1A an attractive pharmacological strategy. Methods: A phenotypic drug screening strategy coupled with multi-omics approaches was utilized to rapidly identify a molecular glue degrader for CORO1A and to uncover the associated mechanisms. The Omics and Text-based Target Enrichment and Ranking (OTTER) tools, co-immunoprecipitation (Co-IP) assay, mass spectrometry, and the separation of phases-based protein interaction reporter (SPPIER) method were employed to explore the interaction between Aurovertin B (AB) and CORO1A via TRIM4. The pharmacological effects of AB were assessed using TNBC patient-derived organoids (PDOs) and 3D bioprinting models. Results: We identified AB as a previously undisclosed molecular glue that significantly promotes the neddylation and proteasomal degradation of CORO1A via TRIM4, an atypical E3 ligase. Notably, the degradation of CORO1A markedly inhibited various cellular processes and exerted robust antitumor effects in TNBC PDOs and 3D bioprinting models. Conclusions: Our findings underscore the critical role of CORO1A in TNBC and lay a crucial foundation for the development of innovative drugs based on molecular glue technology.

01 Sep 2024·Cell Reports

The TRIM4 E3 ubiquitin ligase degrades TPL2 and is modulated by oncogenic KRAS

Article

Author: Adhikari, Hema ; Dodhiawala, Paarth B ; Lim, Kian-Huat ; Townsend, Reid ; Dodhiawala, Paarth B. ; Geng, Yutong ; Bansod, Sapana ; Grierson, Patrick M ; Grierson, Patrick M. ; Held, Jason M ; Held, Jason M. ; Liu, Peng ; Bulle, Ashenafi ; Li, Lin

Loss-of-function mutations in the C terminus of TPL2 kinase promote oncogenesis by impeding its proteasomal degradation, leading to sustained protein expression. However, the degradation mechanism for TPL2 has remained elusive. Through proximity-dependent biotin identification (BioID), we uncovered tripartite motif-containing 4 (TRIM4) as the E3 ligase that binds and degrades TPL2 by polyubiquitination of lysines 415 and 439. The naturally occurring TPL2 mutants R442H and E188K exhibit impaired TRIM4 binding, enhancing their stability. We further discovered that TRIM4 itself is stabilized by another E3 ligase, TRIM21, which in turn is regulated by KRAS. Mutant KRAS recruits RNF185 to degrade TRIM21 and subsequently TRIM4, thereby stabilizing TPL2. In the presence of mutant KRAS, TPL2 phosphorylates and degrades GSK3β, resulting in β-catenin stabilization and activation of the Wnt pathway. These findings elucidate the physiological mechanisms regulating TPL2 and its exploitation by mutant KRAS, underscoring the need to develop TPL2 inhibitors for KRAS-mutant cancers.

Analysis

Perform a panoramic analysis of this field.

view full example data

Hiro LS Researcher

The AI Search Engine Built to Accelerate Biopharma Decisions

Search across billion-scale life sciences data to uncover signals, validate evidence, and act with confidence.

Ask any biopharma research question→

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, Patsnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Discover Synapse Data Servers

Synapse data is now integrated into the PatSnap LS Model Context Protocol (MCP) service. Customize your LLM agent now using our MCP server!

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

TRIM4

Basic Info

Related

Analysis