Last update 01 Nov 2024

PGAM5

Last update 01 Nov 2024

Basic Info

Synonyms

Bcl-XL-binding protein v68, BXLBv68, MGC5352

+ [4]

Introduction

Displays phosphatase activity for serine/threonine residues, and, dephosphorylates and activates MAP3K5 kinase. Has apparently no phosphoglycerate mutase activity. May be regulator of mitochondrial dynamics. Substrate for a KEAP1-dependent ubiquitin ligase complex. Contributes to the repression of NFE2L2-dependent gene expression. Acts as a central mediator for programmed necrosis induced by TNF, by reactive oxygen species and by calcium ionophore.

Drugs associated with PGAM5

LFHP-1c

Target

PGAM5

Mechanism

PGAM5 inhibitors

Active Org.

Guangdong Longfu Medicine Co. Ltd.

Originator Org.

Guangdong Longfu Medicine Co. Ltd.

Active Indication

Ischemic stroke

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with PGAM5

100 Translational Medicine associated with PGAM5

0 Patents (Medical) associated with PGAM5

240

Literatures (Medical) associated with PGAM5

01 Dec 2024·Computational and Structural Biotechnology Journal

Identification and validation of protein biomarkers for predicting gastrointestinal stromal tumor recurrence

Article

Author: Li, Jie ; He, Yixuan ; Kang, Weiming ; Sun, Juan ; Ye, Xin

We conducted a proteomic analysis using mass spectrometry to identify and validate protein biomarkers for accurately predicting recurrence risk in gastrointestinal stromal tumors (GIST) patients, focusing on differentially expressed proteins in metastatic versus primary GIST tissues. We selected five biomarkers-GPX4, RBM4, TPM3, PFKFB2, and PGAM5-and validated their expressions in primary tumors of recurrent and non-recurrent GIST patients via immunohistochemistry. Our analysis of the association between these biomarkers with recurrence-free survival (RFS) and overall survival (OS), along with their interrelationships, revealed that immunohistochemistry confirmed significantly higher expressions of these biomarkers in primary GIST tissues of recurrent patients. Kaplan-Meier survival analysis showed that high expressions of GPX4, RBM4, TPM3, PFKFB2, and PGAM5 correlated with lower RFS, and GPX4 and RBM4 with lower OS. All biomarker pairs showed positive associations, with high expressions correlating with increased recurrence rates, and GPX4 and RBM4 with higher mortality rates. In conclusion, the biomarkers GPX4, RBM4, TPM3, PFKFB2, and PGAM5 are clinically relevant for predicting GIST recurrence, with their high expressions in primary tumors linked to poorer RFS and OS. They serve as potential prognostic indicators, enabling early treatment and improved outcomes. The observed interrelationships among these biomarkers further validate their accuracy in predicting GIST recurrence.

01 Dec 2024·Brain Research

The KEAP1/PGAM5/AIFM1-Mediated oxeiptosis pathway in Alzheimer’s disease

Article

BACKGROUNDAlzheimer's Disease (AD) is a neurodegenerative disease with mitochondrial dysfunction and oxidative stress. Oxeiptosis is a cell death pathway sensitive to reactive oxygen species (ROS). This study investigates the role of oxeiptosis pathway and mitochondrial damage in AD.METHODSAn AD model was developed in C57BL/6 mice by injecting Aβ_1-42 oligomers into the brain. Cognitive function was tested using the Morris water maze. Exposure of HT22 mouse hippocampal neurons to H₂O₂ induces oxidative stress. Protein levels of KEAP1, PGAM5 and AIFM1 were analyzed by western blot, and mitochondrial damage was observed with electron microscopy. Cell survival rates were using the CCK8 assay and flow cytometry after knocking down KEAP1, PGAM5 and AIFM1.RESULTSThe protein concentrations of KEAP1, PGAM5 and AIFM1 were found to be elevated in the hippocampal tissues of AD mice compared to control group, accompanied by mitochondrial damage in the hippocampal neurons of the AD group. Similarly, in the HT22 oxidative stress model, there was an increase in the protein levels of KEAP1, PGAM5 and AIFM1, along with observed mitochondrial damage. Following individual and combined knockdown of KEAP1, PGAM5 and AIFM1, cell survival rates under oxidative stress conditions were higher compared to H₂O₂ group, with no significant difference in cell survival rates among the knockdown groups.CONCLUSIONThis research underscores the critical role of the KEAP1/PGAM5/AIFM1-mediated oxeiptosis pathway in neuronal cell death, offering insights into potential therapeutic targets for mitigating neurodegeneration in AD.

02 Oct 2024·Autophagy

PGAM5 interacts with and maintains BNIP3 to license cancer-associated muscle wasting

Article

Author: Yan, Xinyi ; Lai, Nianhong ; Gao, Baogui ; Gu, Anna Meilin ; Sun, Xuegang ; La, Lei ; Han, Qinrui ; Zhang, Qingyuan ; Chen, Chunhui ; Zhang, Qingling ; Wang, Hao ; Ma, Ye

Regressing the accelerated degradation of skeletal muscle protein is a significant goal for cancer cachexia management. Here, we show that genetic deletion of Pgam5 ameliorates skeletal muscle atrophy in various tumor-bearing mice. pgam5 ablation represses excessive myoblast mitophagy and effectively suppresses mitochondria meltdown and muscle wastage. Next, we define BNIP3 as a mitophagy receptor constitutively associating with PGAM5. bnip3 deletion restricts body weight loss and enhances the gastrocnemius mass index in the age- and tumor size-matched experiments. The NH₂-terminal region of PGAM5 binds to the PEST motif-containing region of BNIP3 to dampen the ubiquitination and degradation of BNIP3 to maintain continuous mitophagy. Finally, we identify S100A9 as a pro-cachectic chemokine via activating AGER/RAGE. AGER deficiency or S100A9 inhibition restrains skeletal muscle loss by weakening the interaction between PGAM5 and BNIP3. In conclusion, the AGER-PGAM5-BNIP3 axis is a novel but common pathway in cancer-associated muscle wasting that can be targetable. Abbreviation: AGER/RAGE: advanced glycation end-product specific receptor; BA1: bafilomycin A₁; BNIP3: BCL2 interacting protein 3; BNIP3L: BCL2 interacting protein 3 like; Ckm-Cre: creatinine kinase, muscle-specific Cre; CM: conditioned medium; CON/CTRL: control; CRC: colorectal cancer; FUNDC1: FUN14 domain containing 1; MAP1LC3A/LC3A: microtubule associated protein 1 light chain 3 alpha; PGAM5: PGAM family member 5, mitochondrial serine/threonine protein phosphatase; S100A9: S100 calcium binding protein A9; SQSTM1/p62: sequestosome 1; TOMM20: translocase of outer mitochondrial membrane 20; TIMM23: translocase of inner mitochondrial membrane 23; TSKO: tissue-specific knockout; VDAC1: voltage dependent anion channel 1.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

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.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

PGAM5

Basic Info

Related

Analysis