The p23 protein performs a significant function in maintaining cellular health. This protein participates in various fundamental processes that ensure the proper functioning of our cells. It impacts how other cellular components behave and interact.
Understanding P23
P23 is classified as a co-chaperone protein, assisting other larger proteins, known as chaperones. It is associated with Heat Shock Protein 90 (Hsp90), a molecular chaperone involved in the proper folding and stabilization of a wide array of client proteins.
P23 primarily regulates Hsp90’s activity. It facilitates the adenosine triphosphate (ATP)-driven cycle of Hsp90, enabling Hsp90 to bind and process its client proteins. P23 enters this cycle at a later stage, enhancing the maturation of these client proteins. This small protein is found ubiquitously across various organisms, from yeast to humans.
How P23 Functions in Our Cells
P23 ensures the stability and proper function of numerous “client proteins” that rely on Hsp90 for their maturation. These include steroid hormone receptors, such as the estrogen and androgen receptors, which are crucial for cellular signaling. P23 enhances their ability to bind hormones, supporting their active state.
Beyond hormone receptors, p23 also influences proteins involved in cell growth and survival pathways, including Fes tyrosine kinase, heme-regulated kinase HRI, and the transcription factor Hsf1. It is also linked to polymerases like telomerase and hepadnavirus reverse transcriptase. While p23 can bind to a specific conformational state of Hsp90, its direct interaction with these diverse client proteins, independent of Hsp90, is a subject of ongoing research.
P23 acts as a regulator, modulating the activity of other proteins rather than performing direct enzymatic functions itself. It stabilizes an ATP-dependent conformational state of Hsp90, which increases Hsp90’s affinity for its client proteins. This contributes to the proper folding and activation of its client proteins, thereby influencing processes like cell cycle progression and cellular responses to stress.
P23’s Role in Health and Illness
The functions of p23 have significant implications for human health, particularly in the context of various diseases where protein folding and stability are compromised. In cancer, for instance, the interaction between p23, Hsp90, and their client proteins can directly influence cell proliferation, survival, and a cell’s resistance to therapeutic drugs. Many Hsp90 client proteins are involved in oncogenic survival signaling, making p23 a potential target in cancer research.
P23’s involvement extends to neurodegenerative diseases, where protein misfolding and aggregation are hallmarks of the conditions. While its exact role in these diseases is still being explored, research suggests that proper levels of p23 expression are important for neuronal function. For example, even a 50% increase in p23 levels in the central nervous system of mice has been shown to cause neurological problems, including tremors and uncoordinated movements. This highlights how disruptions in p23’s chaperone-assisting role can contribute to disease pathology, underscoring its broad impact on cellular proteostasis.