PSMB4

Overview

PSMB4 (Proteasome Subunit Beta Type-4) is a protein that in humans is encoded by the PSMB4 gene. It is a component of the 20S core proteasome complex, which is involved in the degradation of ubiquitinated proteins. This process is crucial for maintaining cellular protein homeostasis by removing damaged or misfolded proteins and regulating the concentration of specific proteins to control various cellular processes.

Structure

The PSMB4 protein is a part of the beta subunit family of the proteasome complex. The 20S proteasome is a barrel-shaped structure composed of four stacked rings, each containing seven subunits. The two outer rings consist of alpha subunits, while the two inner rings are composed of beta subunits, including PSMB4. The beta subunits possess proteolytic activity, which is essential for the proteasome's function in protein degradation.

Function

PSMB4 plays a critical role in the proteolytic function of the proteasome. It contributes to the cleavage of peptide bonds in proteins that have been tagged for degradation by ubiquitin. This process is ATP-dependent and occurs in the cytoplasm and nucleus of eukaryotic cells. The proteasome degrades proteins into small peptides, which can then be further broken down into amino acids or presented on the cell surface by MHC class I molecules for immune surveillance.

Clinical Significance

Alterations in the function or expression of PSMB4 have been implicated in various diseases, including cancer and neurodegenerative disorders. Overexpression of PSMB4 has been observed in certain types of cancer, suggesting a role in tumor progression and resistance to apoptosis. Conversely, reduced proteasome activity, potentially involving PSMB4, has been associated with neurodegenerative diseases such as Alzheimer's and Parkinson's disease, where the accumulation of misfolded proteins is a hallmark.

Research and Therapeutic Implications

Given its central role in protein degradation, PSMB4 and the proteasome complex are targets for therapeutic intervention. Proteasome inhibitors, such as bortezomib, have been developed and are used in the treatment of multiple myeloma and certain lymphomas. These inhibitors work by blocking the proteolytic activity of the proteasome, leading to the accumulation of proteins that induce apoptosis in cancer cells.

Also see

• Proteasome
• Ubiquitin-proteasome system
• Protein degradation
• Bortezomib
• Cancer
• Neurodegenerative diseases

PSMB4
Identifiers
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