SLC7A11

Overview

SLC7A11 is a gene that encodes a protein known as the solute carrier family 7 member 11. This protein is a component of the cystine/glutamate antiporter system, commonly referred to as system Xc−. The primary function of this antiporter is to mediate the exchange of extracellular cystine and intracellular glutamate across the plasma membrane.

Structure

The SLC7A11 protein is a transmembrane protein that forms a heterodimer with the SLC3A2 protein, also known as 4F2hc. This heterodimer is essential for the proper functioning of the cystine/glutamate antiporter. The SLC7A11 subunit is responsible for the transport activity, while the SLC3A2 subunit is necessary for the stability and localization of the transporter on the cell membrane.

Function

SLC7A11 plays a crucial role in maintaining cellular redox balance by facilitating the uptake of cystine, which is subsequently reduced to cysteine. Cysteine is a precursor for the synthesis of glutathione, a major antioxidant that protects cells from oxidative stress. By exporting glutamate in exchange for cystine, SLC7A11 also regulates extracellular glutamate levels, which can influence neurotransmission and excitotoxicity in the nervous system.

Clinical Significance

Alterations in SLC7A11 expression and function have been implicated in various diseases. Overexpression of SLC7A11 is often observed in cancer cells, where it contributes to chemoresistance by enhancing glutathione synthesis and reducing oxidative stress. Conversely, reduced activity of SLC7A11 can lead to increased oxidative stress and cell death, which is relevant in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Parkinson's disease.

Regulation

The expression of SLC7A11 is regulated by several factors, including the transcription factor NRF2, which is activated in response to oxidative stress. Additionally, the tumor suppressor p53 can repress SLC7A11 expression, linking it to cellular stress responses and apoptosis.

Research Directions

Current research on SLC7A11 focuses on its role in cancer metabolism and resistance to therapy, as well as its potential as a therapeutic target. Inhibitors of SLC7A11 are being explored as a means to sensitize cancer cells to chemotherapy and radiation by disrupting their redox balance.

Also see

• Glutathione
• Oxidative stress
• Cystine/glutamate antiporter
• Neurodegenerative diseases
• Cancer metabolism