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Last update 08 May 2025

TLE3

Last update 08 May 2025

Basic Info

Synonyms

Enhancer of split groucho-like protein 3, ESG, ESG3

+ [6]

Introduction

Transcriptional corepressor that binds to a number of transcription factors (PubMed:28689657). Inhibits the transcriptional activation mediated by CTNNB1 and TCF family members in Wnt signaling (PubMed:28689657). The effects of full-length TLE family members may be modulated by association with dominant-negative AES (By similarity).

Drugs associated with TLE3

CCT-717

Target

CB1R x TLE3

Mechanism

CB1 antagonists [+1]

Active Org.

Canary Cure Therapeutics Inc

Originator Org.

Canary Cure Therapeutics Inc

Active Indication

Obesity

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

CCT-617

Target

TLE3

Mechanism

TLE3 inhibitors

Active Org.

Canary Cure Therapeutics Inc

Originator Org.

Canary Cure Therapeutics Inc

Active Indication

Obesity

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with TLE3

100 Translational Medicine associated with TLE3

0 Patents (Medical) associated with TLE3

147

Literatures (Medical) associated with TLE3

01 Apr 2025·Advanced Science

TRIM56 Promotes White Adipose Tissue Browning to Attenuate Obesity by Degrading TLE3

Article

Author: Huang, Kai ; Du, Meng ; Qin, Haojie ; Zhong, Yi ; Miao, Yanli ; Huang, Jinhui

AbstractIn mammals, the activation of thermogenic adipocytes, such as beige and brown adipocytes, can significantly increase overall energy expenditure, offering a promising strategy to combat metabolic diseases. Despite its considerable potential, the regulatory mechanisms governing this activation remain largely elusive. This study bridges this gap by elucidating that tripartite motif 56 (TRIM56), an E3 ubiquitin ligase, is upregulated in response to cold stimuli, thereby promoting the recruitment of beige adipocytes. Notably, the overexpression of TRIM56 in adipocytes is shown to help mice maintain a core temperature under cold conditions, as well as confer protection against diet‐induced obesity. Mechanistically, TRIM56 facilitates the degradation of the transducin‐like enhancer protein 3 (TLE3) protein by promoting its K48‐linked ubiquitination, which subsequently triggers the activation of thermogenic genes in subcutaneousl white adipose tissue and improved the metabolic profiles. These findings unveil a novel function for TRIM56 in adipocyte browning, suggesting its potential as a therapeutic target for the treatment of metabolic disorders.

01 Mar 2025·Journal of Advanced Research

Transducin-like enhancer of split 3 protects against lipopolysaccharide-induced inflammation through DEAD-box helicase 5–activating transcription factor 1–protein phosphatase 2 regulatory subunit 5A signaling

Article

Author: Dong, Yin ; Zhong, Yi ; Fan, Di ; Du, Meng ; Huang, Kai ; Li, Xiaoguang

INTRODUCTIONSepsis consists of life-threatening multi-organ dysfunction caused by an excessive systemic inflammatory response to infection. Therefore, identifying negative regulators of innate inflammation is crucial for treating this condition.OBJECTIVESIn this study, we aimed to understand how transducin-like enhancer of split 3 (TLE3) regulates inflammatory responses.METHODSWe detected Tle3 changes in sepsis patients by analyzing public databases, which were confirmed in septic survivors, septic mouse models, and inflammatory macrophages using Western blotting, qRT-PCR, and immunohistochemistry staining. We investigated the role and mechanism of TLE3 in sepsis by utilizing bone marrow-transplantation (BMT) and adenovirus-infected mice. Furthermore, Protein-Protein Docking, BiFC, LC-MS/MS analysis, CUT & Tag-seq, and CHIP experiments were utilized to disclose the mechanism underlying TLE3 involving macrophage inflammation.RESULTSIn this study, we found that Tle3 transcript is upregulated in peripheral blood samples of sepsis survivors and is decreased in non-survivors, suggesting the critical role of TLE3 in sepsis outcomes. TLE3 is also upregulated in lipopolysaccharide (LPS)-stimulated human monocyte-derived macrophages (MDMs), murine bone marrow-derived macrophages (BMDMs), and septic mice. Gain-of- and loss-of-function of TLE3 in LPS-stimulated murine BMDMs, human MDMs, and mouse models of sepsis showed that TLE3 alleviates LPS-induced cytokine production, as well as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) activation in macrophages, which protects against LPS-induced acute systemic inflammation, multi-organ injury, and death caused by sepsis. Mechanistically, upregulated TLE3 interacts with the transcriptional coactivator, DEAD-box helicase 5 (DDX5), promoting its retention in the cytoplasm and ultimately decreasing transcription of the DDX5/ activating transcription factor 1 (ATF1)-targeted gene Ppp2r5a. Furthermore, the TLE3-DDX5-ATF1 axis downregulates PPP2R5A, a negative regulatory subunit of protein phosphatase 2A (PP2A), thereby increasing PP2A activity and promoting the dephosphorylation of NF-κB and MAPK.CONCLUSIONOur study shows that TLE3 represents a novel suppressor of LPS-induced inflammatory signaling in macrophages.

01 Sep 2024·Immunity, Inflammation and Disease

Efficacy and mechanism of action of ginsenoside Rg3 on radiation proctitis in rats

Article

Author: Lin, Lili ; Dai, Jiuju ; Cai, Hongyi ; Li, Xuxia ; Hu, Tingting ; Duan, Xiaoyu

AbstractObjectiveRadiation proctitis (RP) refers to rectal injury caused by radiation treatment of pelvic and retroperitoneal malignancies, which has a major impact on the treatment prognosis and quality of life of patients with cancer. The tetracyclic triterpene saponin monomer ginsenoside Rg3 (GRg3), the primary bioactive ingredient in ginseng extracts, has therapeutic effects against RP in rats. Here, we validated its efficacy and elucidated its mechanism of action.MethodsA rat RP model was established in 48 Wistar rats. Rats were randomly divided into control (untreated), irradiation, irradiation + dexamethasone, and irradiation + GRg3 (low‐, medium‐, and high‐dose) groups. After 2 weeks' treatment, serum IL‐4, IL‐10, and TNF‐α levels were tested by enzyme‐linked immunosorbent assays. In rectal tissue, Ikbkb, Ikka, and Casp8 mRNA expression was detected by a reverse transcription‐quantitative polymerase chain reaction. IKK‐β, IκB‐α, p‐IκB‐α, p50, and caspase‐8 protein levels were determined by western blot analysis.ResultsGRg3 significantly improved the general condition and histopathological damage in rats with RP. Moreover, GRg3 decreased the levels of factors that promote inflammation (TNF‐α) and increased the levels of factors that reduce inflammation (IL‐4 and IL‐10). GRg3 markedly reduced the activation of NF‐κB and caspase‐8 signaling pathways.ConclusionsThus, GRg3 may reduce the inflammatory response by blocking the NF‐κB signaling pathway and improving the balance of inflammation‐related factors. GRg3 may also inhibit intestinal cell apoptosis by suppressing the TNF‐α/caspase‐8 signaling cascade, thereby reducing radiological rectal injury. Our results verify that GRg3 is a promising therapeutic agent for RP treatment and shed light on its mechanism.

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TLE3

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