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Last update 08 May 2025

TRIM35

Last update 08 May 2025

Basic Info

Synonyms

E3 ubiquitin-protein ligase TRIM35, Hemopoietic lineage switch protein 5, HLS5

+ [4]

Introduction

E3 ubiquitin-protein ligase that participates in multiple biological processes including cell death, glucose metabolism, and in particular, the innate immune response. Mediates 'Lys-63'-linked polyubiquitination of TRAF3 thereby promoting type I interferon production via RIG-I signaling pathway (PubMed:32562145). Can also catalyze 'Lys-48'-linked polyubiquitination and proteasomal degradation of viral proteins such as influenza virus PB2 (PubMed:32562145). Acts as a negative feedback regulator of TLR7- and TLR9-triggered signaling. Mechanistically, promotes the 'Lys-48'-linked ubiquitination of IRF7 and induces its degradation via a proteasome-dependent pathway (PubMed:25907537). Reduces FGFR1-dependent tyrosine phosphorylation of PKM, inhibiting PKM-dependent lactate production, glucose metabolism, and cell growth (PubMed:25263439).

Drugs associated with TRIM35

CN115851624

Patent Mining

Target

TRIM35

Mechanism-

Active Org.

Xuzhou Medical University

Originator Org.

Xuzhou Medical University

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with TRIM35

100 Translational Medicine associated with TRIM35

0 Patents (Medical) associated with TRIM35

Literatures (Medical) associated with TRIM35

01 Mar 2025·Advanced Science

Endothelial TRIM35‐Regulated MMP10 Release Exacerbates Calcification of Vascular Grafts

Article

Author: Tan, Qian ; Lu, Jun ; Huang, Peiyuan ; Liu, Yuanyuan ; Lu, Yao ; Leng, Yiming ; Cai, Jingjing ; Wang, Jie ; Chen, Jingyuan ; Wang, Wei ; Chen, Xuliang ; Yang, Wenjing ; Xu, Qingbo ; Yuan, Hong ; Li, Yalan ; Weng, Liang ; Jiang, Youxiang

AbstractVascular calcification is a highly regulated process in cardiovascular disease (CVD) and is strongly correlated with morbidity and mortality, especially in the adverse stage of vascular remodeling after coronary artery bypass graft surgery (CABG). However, the pathogenesis of vascular graft calcification, particularly the role of endothelial‐smooth muscle cell interaction, is still unclear. To test how ECs interact with SMCs in artery grafts, single‐cell analysis of wild‐type mice is first performed using an arterial isograft mouse model and found robust cytokine‐mediated signaling pathway activation and SMC proliferation, together with upregulated endothelial tripartite motif 35 (TRIM35) expression. Unexpectedly, severe SMC calcification in artery grafts is found in TRIM35 conditional endothelial knockout (cKO) mice. Calcified medium (comprising calcium chloride and beta‐glycerophosphate)‐induced calcium deposition in vitro is also found in SMCs cocultured with TRIM35 knockout endothelium. This extraordinary phenomenon is further confirmed to be induced by increased MMP10 secretion. Mechanistically, endothelial TRIM35 inhibits MMP10 expression and secretion by promoting K63‐linked ubiquitination of RelB and maintaining its nuclear localization, consequently inhibiting nuclear transcription of MMP10 through the noncanonical NF‐κB signaling pathway. Targeting MMP10 in situ in arterial isografts can effectively alleviate vascular calcification caused by conditional endothelial TRIM35 knockout. These findings demonstrated that TRIM35 inhibited vascular calcification during arterial isograft remodeling, a process that is driven by the aberrant secretion of endothelial MMP10. Targeting MMP10 pathway may be a potential therapeutic strategy for vascular calcification in vessel grafts.

05 Jul 2024·Circulation Research

TRIM35 Monoubiquitinates H2B in Cardiac Cells, Implications for Heart Failure

Article

Author: Zhao, Yuan Yuan ; Bowles, Dawn E. ; Sutendra, Gopinath ; Nanoa, Joseph ; Michelakis, Evangelos D. ; Mendiola Pla, Michelle ; Liu, Yongsheng ; Huang, Guocheng ; Tejay, Saymon ; Kinnaird, Adam ; Haromy, Alois ; Lorenzana-Carrillo, Maria Areli

BACKGROUND:The tumor suppressor and proapoptotic transcription factor P53 is induced (and activated) in several forms of heart failure, including cardiotoxicity and dilated cardiomyopathy; however, the precise mechanism that coordinates its induction with accessibility to its transcriptional promoter sites remains unresolved, especially in the setting of mature terminally differentiated (nonreplicative) cardiomyocytes.METHODS:Male and female control or TRIM35 (tripartite motif containing 35) overexpression adolescent (aged 1–3 months) and adult (aged 4–6 months) transgenic mice were used for all in vivo experiments. Primary adolescent or adult mouse cardiomyocytes were isolated from control or TRIM35 overexpression transgenic mice for all in vitro experiments. Adenovirus or small-interfering RNA was used for all molecular experiments to overexpress or knockdown, respectively, target genes in primary mouse cardiomyocytes. Patient dilated cardiomyopathy or nonfailing left ventricle samples were used for translational and mechanistic insight. Chromatin immunoprecipitation and DNA sequencing or quantitative real-time polymerase chain reaction (qPCR) was used to assess P53 binding to its transcriptional promoter targets, and RNA sequencing was used to identify disease-specific signaling pathways.RESULTS:Here, we show that E3-ubiquitin ligase TRIM35 can directly monoubiquitinate lysine-120 (K120) on histone 2B in postnatal mature cardiomyocytes. This epigenetic modification was sufficient to promote chromatin remodeling, accessibility of P53 to its transcriptional promoter targets, and elongation of its transcribed mRNA. We found that increased P53 transcriptional activity (in cardiomyocyte-specific Trim35 overexpression transgenic mice) was sufficient to initiate heart failure and these molecular findings were recapitulated in nonischemic human LV dilated cardiomyopathy samples.CONCLUSIONS:These findings suggest that TRIM35 and the K120Ub-histone 2B epigenetic modification are molecular features of cardiomyocytes that can collectively predict dilated cardiomyopathy pathogenesis.

05 Jul 2024·Circulation Research

TRIM35: A Proposed Gateway to p53-Induced Heart Failure Pathogenesis

Article

Author: Foo, Roger S.-Y. ; Lee, Chang Jie Mick

A review.In this issue of Circulation Research, Lorenzana-Carrillo et al performed an unbiased immunoprecipitation mass spectrometry screen for ubiquitinated proteins in a cardiomyocyte-specific TRIM35 overexpression transgenic mice, uncovering lysine-120 (K120) on histone 2B (^K120Ub-H2B) as a target of TRIM35.Likewise, PKM2, as a known ubiquitin candidate of TRIM35, downregulated in HF, was also identified from the screen.Despite increased ^K120Ub-H2B in the TRIM35 overexpression mouse, both transcript and protein expression of p21 and Puma was also far more significantly elevated only in adult and not adolescent mouse cardiomyocytes.Since TRIM35 overexpression is itself critical for stabilizing p53 protein levels via the degradation of MDM2 and ubiquitination of nuclear PKM2,5 the current study has highlighted that ^K120Ub-H2B precedes the stabilization of p53 protein levels, in the initial transcription of p53-target genes such as Puma and p21.In summary, Lorenzana-Carrillo et al have revealed the epigenetic mechanism of ^K120Ub-H2B as a direct target of TRIM35, downstream to its transcriptional regulation, and therebythe multifaceted roles of TRIM35 in stabilizing p53 and its transcriptional targets.

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TRIM35

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