Last update 01 Nov 2024

TRIM72

Last update 01 Nov 2024

Basic Info

Synonyms

MG53, Mitsugumin-53, TRIM72

+ [2]

Introduction

Muscle-specific protein that plays a central role in cell membrane repair by nucleating the assembly of the repair machinery at injury sites. Specifically binds phosphatidylserine. Acts as a sensor of oxidation: upon membrane damage, entry of extracellular oxidative environment results in disulfide bond formation and homooligomerization at the injury site. This oligomerization acts as a nucleation site for recruitment of TRIM72-containing vesicles to the injury site, leading to membrane patch formation. Probably acts upstream of the Ca(2+)-dependent membrane resealing process. Required for transport of DYSF to sites of cell injury during repair patch formation. Regulates membrane budding and exocytosis. May be involved in the regulation of the mobility of KCNB1-containing endocytic vesicles (By similarity).

Drugs associated with TRIM72

rhMG53

Target

TRIM72

Mechanism

TRIM72 modulators [+1]

Active Org.

The Ohio State University

Originator Org.

The Ohio State University

Active Indication

Acute Kidney Injury

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

rhMG53-C14A

Target

TRIM72

Mechanism

TRIM72 modulators

Active Org.

Peking University

Originator Org.

Peking University

Active Indication

Myocardial injury

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

Recombinant human MG53 protein(Merck)

Target

TRIM72

Mechanism

TRIM72 modulators

Active Org.

Merck & Co., Inc.

Originator Org.

Merck & Co., Inc.

Active Indication

Acute Lung Injury

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with TRIM72

100 Translational Medicine associated with TRIM72

0 Patents (Medical) associated with TRIM72

227

Literatures (Medical) associated with TRIM72

01 Dec 2024·Translational Oncology

MG53 suppresses tumor growth via transcriptional inhibition of KIF11 in pancreatic cancer

Article

Author: He, Xiangfei ; Gao, Tong ; Wang, Xiao-Liang ; Zhou, Xinyu ; Cai, Chuanxi ; Cruz-Monserrate, Zobeida ; Tsung, Allan ; Ma, Jianjie

Pancreatic ductal adenocarcinoma (PDAC) poses a formidable challenge in oncology due to its limited treatment options and poor long-term survival rates. Our previous work identified MG53, a member of the tripartite motif family protein (TRIM72), as a key player in tissue repair with potential applications in regenerative medicine. Despite the focus on MG53's cytosolic functions, its nuclear role in suppressing pancreatic cancer remains unknown. Through orthotopic and subcutaneous transplantation studies in mice, we observed enhanced tumor growth in MG53-deficient mice compared to wild-type counterparts. The overexpression of KIF11, a motor protein crucial for cell mitosis regulation, has been linked to the aggressive proliferation of pancreatic cancer cells. Confocal imaging confirmed MG53's presence in the nucleus of human pancreatic cancer cells, while functional assays demonstrated its impact on KIF11 expression and subsequent cell proliferation. Mechanistically, we revealed MG53's transcriptional control over KIF11, leading to cell cycle arrest. Our findings position MG53 as a promising tumor suppressor in PDAC, offering a novel avenue for therapeutic intervention by regulating KIF11 expression.

01 Oct 2024·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

p85α deficiency alleviates ischemia-reperfusion injury by promoting cardiomyocyte survival

Article

Author: Li, Jingchen ; Guo, Jing ; Liu, Yangli ; Dai, Rilei ; Zhu, Wenting ; Ju, Yingjiao ; Zhu, Kun ; Du, Leilei ; Wang, Xun ; Lin, Zhiheng ; Cao, Chun-Mei ; Wang, Li

Myocardial ischemia-reperfusion (I/R) injury is a prevalent cause of myocardial injury, involving a series of interconnected pathophysiological processes. However, there is currently no clinical therapy for effectively mitigating myocardial I/R injury. Here, we show that p85α protein levels increase in response to I/R injury through a comprehensive analysis of cardiac proteomics, and confirm this in the I/R-injured murine heart and failing human myocardium. Genetic inhibition of p85α in mice activates the Akt-GSK3β/Bcl-x(L) signaling pathway and ameliorates I/R-induced cardiac dysfunction, apoptosis, inflammation, and mitochondrial dysfunction. p85α silencing in cardiomyocytes alleviates hypoxia-reoxygenation (H/R) injury through activating the Akt-GSK3β/Bcl-x(L) signaling pathway, while its overexpression exacerbates the damage. Mechanistically, the interaction between MG53 and p85α triggers the ubiquitination and degradation of p85α, consequently enhancing Akt phosphorylation and ultimately having cardioprotective effects. Collectively, our findings reveal that substantial reduction of p85α and subsequently activated Akt signaling have a protective effect against cardiac I/R injury, representing an important therapeutic strategy for mitigating myocardial damage.

01 Oct 2024·Free Radical Biology and Medicine

MG53 inhibits ferroptosis by targeting the p53/SLC7A11/GPX4 pathway to alleviate doxorubicin-induced cardiotoxicity

Article

Author: Ma, Heng ; Mu, Nan ; Zhang, Zihui ; Jiang, Wenhua ; Yu, Lu

Doxorubicin (DOX) is an anthracycline medication that is commonly used to treat solid tumors. However, DOX has limited clinical efficacy due to known cardiotoxicity. Ferroptosis is involved in DOX-induced cardiotoxicity (DIC). Although mitsugumin-53 (MG53) has cardioprotective effects and is expected to attenuate myocardial ischemic injury, its ability to inhibit DOX-induced ferroptosis has not been extensively studied. This research aims to investigate the pathophysiological impact of MG53 on DOX induced ferroptosis. Here, MG53 levels were evaluated in relation to the extent of ferroptosis by establishing in vivo and in vitro DIC mouse models. Additionally, myocardial specific MG53 overexpressing mice were used to study the effect of MG53 on cardiac function in DIC mice. The study found that the MG53 expression decreased in DOX treated mouse hearts or cardiomyocytes. However, MG53-overexpressing improved cardiac function in the DIC model and effectively reduced myocardial ferroptosis by increasing solute carrier family 7 member 11 (SLC7A11) and Glutathione peroxidase 4 (GPX4) levels, which were decreased by DOX. Mechanistically, MG53 binds to tumor suppressor 53 (p53) to regulate its ubiquitination and degradation. Ferroptosis induced by DOX was prevented by either MG53 overexpression or p53 knockdown in cardiomyocytes. The modulation of the p53/SLC7A11/GPX4 pathway by overexpression of MG53 can alleviate DOX induced ferroptosis. The study indicates that MG53 can provide protection against DIC by increasing p53 ubiquitination. These results highlight the previously unidentified role of MG53 in inhibiting ferroptosis to prevent DIC.

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TRIM72

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