Proteasome (prosome, Macropain) Subunit, Alpha 1

Proteasome (prosome, macropain) subunit, alpha 1 (PSMA1) is a protein that in humans is encoded by the PSMA1 gene. The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure is composed of 4 rings of 28 non-identical subunits; 2 rings are made up of 7 alpha subunits and 2 rings are made up of 7 beta subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. PSMA1 is a member of the proteasome B-type family, also known as the T1B family, that is a 20S core alpha subunit.

Structure and Function

The proteasome is an enzymatic complex that plays a critical role in intracellular protein degradation and turnover, as well as in the regulation of various cellular processes, including cell cycle progression, apoptosis, and DNA repair. The PSMA1 gene encodes one of the alpha subunits of the 20S core proteasome complex. This subunit is essential for the assembly and activity of the 20S proteasome. The 20S proteasome is a barrel-shaped structure formed by four stacked rings: two identical outer alpha rings and two identical inner beta rings. Each ring is composed of seven distinct subunits, with the alpha subunits forming the outer rings and the beta subunits forming the inner rings. The proteolytic activity of the proteasome is contained within the beta subunits, whereas the alpha subunits are involved in the regulation of substrate entry into the core particle.

Clinical Significance

Alterations in the proteasome system have been implicated in the pathogenesis of various diseases, including cancer, neurodegenerative disorders, and autoimmune diseases. In cancer, the increased activity of the proteasome is believed to contribute to the degradation of tumor suppressor proteins, thereby promoting cancer cell survival and proliferation. Consequently, proteasome inhibitors, such as bortezomib, have been developed as therapeutic agents for the treatment of multiple myeloma and other malignancies. In neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease, impaired proteasome function is thought to lead to the accumulation of misfolded or damaged proteins, which can form toxic aggregates and contribute to neuronal cell death.

Genetic Information

The PSMA1 gene is located on the short (p) arm of chromosome 5 at position 23.3, more precisely at 5p13.1. The gene spans approximately 24 kilobases and consists of 14 exons. The PSMA1 gene produces a 29 kDa protein composed of 263 amino acids. Variants and mutations in the PSMA1 gene have been studied for their association with disease susceptibility and response to proteasome inhibitor therapy.

See Also

• Proteasome
• Ubiquitin
• Proteasome inhibitor
• Multiple myeloma
• Neurodegenerative disorders

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