Selenoproteins are a group of proteins that incorporate the rare amino acid selenocysteine into their structure. Selenocysteine, sometimes called the “21st amino acid,” is encoded by the UGA codon in a unique context that requires specific translational machinery. Many selenoproteins are known for their antioxidant and redox-regulatory functions, which are critical in maintaining cellular homeostasis. These functions help protect cells from oxidative stress and damage—processes that, when dysregulated, can contribute to carcinogenesis.
Roles of Selenoproteins in Cancer.
1. Antioxidant Defense & Redox Regulation
-Glutathione Peroxidases (GPxs): Enzymes like GPX1, GPX2, and GPX3 reduce hydrogen peroxide and lipid hydroperoxides. This protects cells against oxidative DNA damage.
-Thioredoxin Reductases (TXNRDs): TXNRD1, TXNRD2, and TXNRD3 help maintain the reduced state of thioredoxin, thereby contributing to redox homeostasis and cell survival under stress.
2. Cellular Proliferation and Apoptosis
-Selenoproteins may modulate signaling pathways that regulate cell cycle progression and apoptosis. Variations in expression levels—either upregulation or downregulation—can tip the balance toward uncontrolled cell growth or cell death.
The expression of selenoproteins in cancers is complex and can vary by tumor type. Here are some examples:
Glutathione Peroxidases (GPxs)
-GPX1: Both overexpression and underexpression have been reported depending on the tumor context. In some cases, high GPX1 expression can help cancer cells survive oxidative stress.
-GPX2: Often upregulated in colorectal cancer and some GC, poor prognosis.
-GPX3: Typically downregulated in many cancers with tumor progression and poor outcome, suggesting its role as a tumor suppressor.
Thioredoxin Reductases (TXNRDs)
-TXNRD1: Frequently overexpressed in various tumors such as lung, breast, and liver cancers.
High TXNRD1 levels are generally associated with a poor prognosis.
-SELENOP (Selenoprotein P) SELENOP serves as a selenium transport protein and has antioxidant properties. Decreased SELENOP expression has been linked to poorer outcomes in some cancers, possibly due to reduced selenium availability for other protective selenoproteins.
Other Selenoproteins
-SELENOF and SELENOS:
-SELENOM and SELENOK:
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