Last update 01 Nov 2024

TRIM29

Last update 01 Nov 2024

Basic Info

Synonyms

Ataxia telangiectasia group D-associated protein, ATDC, FLJ36085

+ [3]

Introduction

Plays a crucial role in the regulation of macrophage activation in response to viral or bacterial infections within the respiratory tract. Mechanistically, TRIM29 interacts with IKBKG/NEMO in the lysosome where it induces its 'Lys-48' ubiquitination and subsequent degradation. In turn, the expression of type I interferons and the production of pro-inflammatory cytokines are inhibited. Additionally, induces the 'Lys-48' ubiquitination of STING1 in a similar way, leading to its degradation.

Drugs associated with TRIM29

SB-24011

Target

STING x TRIM29

Mechanism

STING1 inhibitors [+1]

Active Org.

Sparkbiopharma Co., Ltd.

Originator Org.

Sparkbiopharma Co., Ltd.

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with TRIM29

100 Translational Medicine associated with TRIM29

0 Patents (Medical) associated with TRIM29

175

Literatures (Medical) associated with TRIM29

01 Nov 2024·International Journal of Cancer

Prelude to malignancy: A gene expression signature in normal mammary gland from breast cancer patients suggests pre‐tumorous alterations and is associated with adverse outcomes

Article

Author: Dumanski, Jan P. ; Piotrowski, Arkadiusz ; Szylberg, Łukasz ; Filipowicz, Natalia ; Kostecka, Anna ; Śrutek, Ewa ; Mieczkowski, Jakub ; Pęksa, Rafał ; Las‐Jankowska, Manuela ; Davies, Hanna ; Horbacz, Monika ; Hartman, Johan ; Nowikiewicz, Tomasz ; Zegarski, Wojciech ; Ławrynowicz, Urszula ; Chojnowska, Katarzyna ; Hoffman, Jacek ; Bruhn‐Olszewska, Bożena ; Andreou, Maria ; Jankowski, Michał ; Maniewski, Mateusz ; Jąkalski, Marcin ; Duzowska, Katarzyna ; Skokowski, Jarosław ; Nowikiewicz, Magdalena ; Jankau, Jerzy ; Bała, Dariusz

AbstractDespite advances in early detection and treatment strategies, breast cancer recurrence and mortality remain a significant health issue. Recent insights suggest the prognostic potential of microscopically healthy mammary gland, in the vicinity of the breast lesion. Nonetheless, a comprehensive understanding of the gene expression profiles in these tissues and their relationship to patient outcomes remain missing. Furthermore, the increasing trend towards breast‐conserving surgery may inadvertently lead to the retention of existing cancer‐predisposing mutations within the normal mammary gland. This study assessed the transcriptomic profiles of 242 samples from 83 breast cancer patients with unfavorable outcomes, including paired uninvolved mammary gland samples collected at varying distances from primary lesions. As a reference, control samples from 53 mammoplasty individuals without cancer history were studied. A custom panel of 634 genes linked to breast cancer progression and metastasis was employed for expression profiling, followed by whole‐transcriptome verification experiments and statistical analyses to discern molecular signatures and their clinical relevance. A distinct gene expression signature was identified in uninvolved mammary gland samples, featuring key cellular components encoding keratins, CDH1, CDH3, EPCAM cell adhesion proteins, matrix metallopeptidases, oncogenes, tumor suppressors, along with crucial genes (FOXA1, RAB25, NRG1, SPDEF, TRIM29, and GABRP) having dual roles in cancer. Enrichment analyses revealed disruptions in epithelial integrity, cell adhesion, and estrogen signaling. This signature, named KAOS for Keratin‐Adhesion‐Oncogenes‐Suppressors, was significantly associated with reduced tumor size but increased mortality rates. Integrating molecular assessment of non‐malignant mammary tissue into disease management could enhance survival prediction and facilitate personalized patient care.

01 Oct 2024·Journal of Cellular and Molecular Medicine

Molecular characterization and biomarker identification in paediatric B‐cell acute lymphoblastic leukaemia

Article

Author: Wang, Chenxuan ; Luo, Linlin ; Wu, Xiaoying ; Zhu, Liuqing ; Sun, Ming ; Du, Yu ; Zhang, Xiankai ; Ou, Qiuxiang ; Lv, Xiaoyan ; Qi, Shanshan ; Long, Fei ; Xiong, Hao ; Yang, Li

AbstractB‐cell acute lymphoblastic leukaemia (B‐ALL) is the most prevalent hematologic malignancy in children and a leading cause of mortality. Managing B‐ALL remains challenging due to its heterogeneity and relapse risk. This study aimed to delineate the molecular features of paediatric B‐ALL and explore the clinical utility of circulating tumour DNA (ctDNA). We analysed 146 patients with paediatric B‐ALL who received systemic chemotherapy. The mutational landscape was profiled in bone marrow (BM) and plasma samples using next‐generation sequencing. Minimal residual disease (MRD) testing on day 19 of induction therapy evaluated treatment efficacy. RNA sequencing identified gene fusions in 61% of patients, including 37 novel fusions. Specifically, the KMT2A‐TRIM29 novel fusion was validated in a boy who responded well to initial therapy but relapsed after 1 year. Elevated mutation counts and maximum variant allele frequency in baseline BM were associated with significantly poorer chemotherapy response (p = 0.0012 and 0.028, respectively). MRD‐negative patients exhibited upregulation of immune‐related pathways (p < 0.01) and increased CD8+ T cell infiltration (p = 0.047). Baseline plasma ctDNA exhibited high mutational concordance with the paired BM samples and was significantly associated with chemotherapy efficacy. These findings suggest that ctDNA and BM profiling offer promising prognostic insights for paediatric B‐ALL management.

01 Oct 2024·Mucosal Immunology

TRIM29 controls enteric RNA virus-induced intestinal inflammation by targeting NLRP6 and NLRP9b signaling pathways

Article

Author: Wang, Junying ; Xing, Junji ; Farhataziz, Naser ; Wang, Ling ; Lu, Wenting ; Gonzalez, Anastasia ; Zhang, Zhiqiang

Infections by enteric virus and intestinal inflammation are recognized as a leading cause of deadly gastroenteritis, and NLRP6 and NLRP9b signaling control these infection and inflammation. However, the regulatory mechanisms of the NLRP6 and NLRP9b signaling in enteric viral infection remain unexplored. In this study, we found that the E3 ligase TRIM29 suppressed type III interferon (IFN-λ) and interleukin-18 (IL-18) production by intestinal epithelial cells (IECs) when exposed to polyinosinic:polycytidylic acid (poly I:C) and enteric RNA viruses. Knockout of TRIM29 in IECs was efficient to restrict intestinal inflammation triggered by the enteric RNA viruses, rotavirus in suckling mice, and the encephalomyocarditis virus (EMCV) in adults. This attenuation in inflammation was attributed to the increased production of IFN-λ and IL-18 in the IECs and more recruitment of intraepithelial protective Ly6A⁺CCR9⁺CD4⁺ T cells in small intestines from TRIM29-deficient mice. Mechanistically, TRIM29 promoted K48-linked ubiquitination, leading to the degradation of NLRP6 and NLRP9b, resulting in decreased IFN-λ and IL-18 secretion by IECs. Our findings reveal that enteric viruses utilize TRIM29 to inhibit IFN-λ and inflammasome activation in IECs, thereby facilitating viral-induced intestinal inflammation. This indicates that targeting TRIM29 could offer a promising therapeutic strategy for alleviating gut diseases.

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TRIM29

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