PSMD8: A Potential Drug Target and Biomarker for Proteasome-Mediated Cellular Signaling

Target Name: PSMD8

NCBI ID: G5714

PSMD8: A Potential Drug Target and Biomarker for Proteasome-Mediated Cellular Signaling

Introduction

Proteasomes, a complex protein-protein machinery that removes damaged or unnecessary proteins from cells, play a crucial role in maintaining cellular homeostasis and regulating various cellular processes. The 26S subunit of the proteasome, also known as PSMD8, is a key component of this complex machinery. It is responsible for degrading proteins into small molecule peptides within cells, thereby maintaining stable protein levels within cells. However, during certain disease processes, functional imbalance of PSMD8 may lead to abnormal protein accumulation, posing serious threats to cells. Therefore, studying the application of PSMD8 in drug treatment and disease diagnosis has important theoretical and practical value.

Structure and function of PSMD8

PSMD8 is a ~200 kilochannel protein that belongs to the hierarchical partner family. Its N-terminus contains an acetylated lysine residue, a common lysine methylation modification that contributes to the interaction of PSMD8 with other proteins. The C-terminus of PSMD8 exposes two conserved cysteine 鈥嬧?媟esidues, which may bind to certain substrates and thereby participate in the function of PSMD8.

PSMD8 is primarily responsible for degrading proteins into small peptides. Under normal circumstances, PSMD8 moves from the cytoplasm to the nucleus along protein-protein complexes and participates in the M-TOR signaling pathway in the cell cycle. When PSMD8 binds to a protein target, it recognizes and binds to a specific region on the target. Next, PSMD8 is denatured, exposing its N- and C-termini, allowing target-binding enzymes to access the active center of PSMD8. Once PSMD8 binds to the target, it will be phosphorylated, thereby activating the target and causing it to undergo phosphorylation modification, leading to protein degradation.

Disease risk of PSMD8

PSMD8 plays an important role in various disease processes, such as cancer, neurodegenerative diseases, and inflammation. In these disease processes, functional imbalance of PSMD8 may lead to abnormal protein accumulation, posing serious threats to cells.

1. Cancer

Many cancers are linked to PSMD8. Studies have found that PSMD8 is involved in the development of a variety of cancers, including liver cancer, lung cancer, breast cancer, and prostate cancer. Variations in PSMD8 are strongly associated with cancer progression and treatment response.

2. Neurodegenerative diseases

Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and Huntington's disease, are closely related to PSMD8 functional imbalance. Studies have found that aberrant expression of PSMD8 in these diseases may lead to abnormal protein accumulation, thereby exacerbating disease progression.

3. Inflammation

Inflammatory diseases, such as rheumatoid arthritis, enteritis, and myocarditis, may also be related to PSMD8. Studies have shown that abnormal expression of PSMD8 in these diseases may lead to an exacerbation of the inflammatory response, thereby exacerbating disease symptoms.

Drug targets for PSMD8

PSMD8 is a potential drug target because many drugs, such as antitumor drugs, anti-inflammatory drugs, and neuroprotective agents, act on the function of PSMD8.

1. Anti-tumor drugs

Anti-tumor drugs, such as alkylating agents, platinum drugs, and anti-metabolite drugs, often exert their anti-tumor effects by inhibiting the activity of PSMD8. Studies have found that inhibition of PSMD8 leads to increased tumor cell growth and spread, thereby increasing tumor invasiveness.

2. Anti-inflammatory drugs

Anti-inflammatory drugs, such as nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids, may also exert their anti-inflammatory effects by inhibiting the activity of PSMD8. Studies have found that inhibition of PSMD8 leads to increased protein degradation at sites of inflammation, thereby exacerbating inflammatory symptoms.

3. Neuroprotective agents

Neuroprotective agents such as

Protein Name: Proteasome 26S Subunit, Non-ATPase 8

Functions: Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair

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