FKBP4

FKBP4 is a protein that in humans is encoded by the FKBP4 gene. This protein is a member of the immunophilin protein family, which play a role in immunoregulation and basic cellular processes involving protein folding and trafficking. FKBP4 is also known as FKBP52, reflecting its molecular weight of approximately 52 kDa. The protein has been implicated in various biological processes, including hormone receptor signaling, protein folding, and neuroprotection.

Function

FKBP4 acts as a co-chaperone with heat shock proteins (HSPs), particularly HSP90. It binds to and regulates steroid hormone receptors, including the progesterone, glucocorticoid, and androgen receptors. This regulation is crucial for the proper functioning of these receptors and, consequently, for the regulation of genes involved in development, metabolism, and the immune response. FKBP4 also plays a role in the folding of newly synthesized proteins and the stabilization of existing proteins, preventing their aggregation and assisting in their proper function.

Clinical Significance

Alterations in the expression or function of FKBP4 have been associated with various diseases. For example, FKBP4 has been implicated in the pathophysiology of neurodegenerative diseases, such as Alzheimer's disease, due to its role in protein folding and its potential to influence tau protein pathology. In cancer, FKBP4 can affect the sensitivity of cancer cells to chemotherapy and hormone therapy, making it a potential target for cancer treatment. Additionally, FKBP4's involvement in steroid hormone receptor signaling suggests it may play a role in conditions sensitive to hormone levels, such as certain reproductive disorders.

Genetic and Molecular Aspects

The FKBP4 gene is located on chromosome 12 in humans. It encodes the FKBP4 protein, which contains a peptidyl-prolyl cis-trans isomerase (PPIase) domain. This domain allows FKBP4 to catalyze the isomerization of peptide bonds at proline residues, which is a critical step in protein folding. The protein also contains tetratricopeptide repeat (TPR) domains, which facilitate its interaction with HSP90, thereby influencing the function of steroid hormone receptors and other client proteins.

Research Directions

Research on FKBP4 continues to explore its potential as a therapeutic target. Given its role in protein folding, FKBP4 inhibitors are being investigated for their potential to modulate protein aggregation, a common feature of neurodegenerative diseases. In cancer, understanding how FKBP4 influences hormone receptor signaling and chemotherapy resistance may lead to new strategies for treatment. Additionally, the role of FKBP4 in reproductive health and its potential impact on fertility and pregnancy-related conditions are areas of ongoing research.

See Also

• Immunophilin
• Heat shock protein
• Steroid hormone receptor
• Protein folding
• Neurodegenerative diseases
• Cancer