TXNDC12 Human
Description
Molecular Structure and Characteristics
TXNDC12 encodes a secretory protein with a conserved thioredoxin fold containing an active-site sequence (CxxC) essential for its enzymatic activity . Key features include:
Redox Regulation and Protein Folding
As a PDI family member, TXNDC12 facilitates disulfide bond formation in client proteins, maintaining sulfhydryl homeostasis and mitigating oxidative stress . It also regulates ER stress responses by interacting with ATF6α during the unfolded protein response .
Ferroptosis Inhibition
TXNDC12 suppresses lipid peroxidation and ferroptosis (iron-dependent cell death) via:
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GSH/GGT7 Axis: Upregulation of glutathione (GSH) synthesis and stabilization of γ-glutamyltransferase 7 (GGT7) .
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Antioxidant Activity: Reducing intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels .
Pancreatic Adenocarcinoma (PAAD)
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Function: Drives proliferation and inhibits ferroptosis. Knockdown reduces clonogenicity by 60% and arrests cell cycle progression .
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Prognostic Value: Elevated TXNDC12 mRNA levels predict shorter survival (log-rank P = 0.003) .
Other Cancers
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Gastric Cancer: Enhances tumorigenicity via FAK/ERK signaling .
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Leukemia: Upregulated in erastin/RSL3-resistant cells; knockdown increases ferroptosis sensitivity .
Key Molecular Pathways
Therapeutic and Prognostic Potential
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Biomarker Potential: High TXNDC12 expression in tumors correlates with advanced stage and metastasis .
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Therapeutic Targeting: Silencing TXNDC12 sensitizes cancer cells to ferroptosis inducers (e.g., erastin) and reduces tumor growth in vivo .
Controversies and Knowledge Gaps
While TXNDC12 is generally oncogenic, one study paradoxically links low TXNDC12 mRNA levels to poor prognosis in lung adenocarcinoma . Further research is needed to clarify tissue-specific roles.
Product Specs
Product Science Overview
Thioredoxin Domain Containing 12 (TXNDC12) is a member of the thioredoxin family, which plays a crucial role in maintaining cellular redox homeostasis. Thioredoxins are small redox proteins that are present in all organisms and are involved in various biological processes, including redox signaling, cell proliferation, and apoptosis .
TXNDC12, like other thioredoxins, contains a characteristic thioredoxin fold and an active site with a conserved CXXC motif. This motif is essential for the protein’s oxidoreductase activity, allowing it to reduce disulfide bonds in other proteins . The reduction of disulfide bonds is a critical process in maintaining protein structure and function, as well as in protecting cells from oxidative stress.
Thioredoxins, including TXNDC12, are involved in various cellular processes. They act as electron donors to peroxidases and ribonucleotide reductase, playing a significant role in DNA synthesis and repair . Additionally, thioredoxins are involved in the regulation of transcription factors and the activation of signaling pathways that control cell growth and survival .
The thioredoxin system consists of thioredoxin, thioredoxin reductase, and NADPH. Thioredoxin reductase is responsible for maintaining thioredoxin in its reduced state, which is necessary for its oxidoreductase activity . This system is crucial for protecting cells from oxidative damage and maintaining redox balance.
Human recombinant TXNDC12 is produced using recombinant DNA technology, which involves inserting the gene encoding TXNDC12 into a suitable expression system, such as bacteria or yeast. This allows for the large-scale production of the protein, which can be used for research and therapeutic purposes.
Human recombinant TXNDC12 is used in various research applications to study its role in cellular processes and its potential therapeutic benefits. For example, it is used to investigate the mechanisms of redox regulation and the development of diseases associated with oxidative stress, such as cancer and neurodegenerative disorders . Additionally, TXNDC12 and other thioredoxins are being explored as potential targets for drug development, aiming to modulate their activity to treat various diseases .
