SFN - stratifin | Elisa - Clia - Antibody - Protein

Background:

YWHAS, also known as 14-3-3 protein sigma, is a member of the 14-3-3 family of proteins, which are highly conserved across eukaryotic species and play critical roles in regulating numerous cellular processes. The 14-3-3 proteins are adaptor proteins that facilitate interactions between phosphorylated serine/threonine residues on target proteins, influencing their function, localization, and stability. YWHAS is specifically involved in cell cycle control, apoptosis, and stress response. It has a unique expression pattern compared to other 14-3-3 isoforms, being particularly significant in epithelial cells and playing a crucial role in the DNA damage response and tumor suppression. Dysregulation of YWHAS is linked to various diseases, including cancer, where it can act as a tumor suppressor.

Protein Structure

YWHAS, like other 14-3-3 proteins, has a conserved structure characterized by:

• Alpha-helical Composition: Each monomer of YWHAS consists of nine alpha helices, which create a stable and rigid structure.
• Dimerization: YWHAS functions as a dimer, which is essential for its activity. The dimeric form allows it to interact simultaneously with multiple target proteins.
• Binding Groove: The dimerization creates a central binding groove that accommodates phosphorylated serine/threonine residues on target proteins.
• Versatile Binding Sites: These sites enable YWHAS to interact with a diverse array of proteins, facilitating its role in various signaling pathways and cellular processes.

Classification and Subtypes

YWHAS is one of the seven mammalian isoforms of the 14-3-3 protein family, which includes β, γ, ε, η, σ (YWHAS), τ, and ζ. Each isoform, while structurally similar, has unique as well as overlapping functions in different tissues and cellular contexts.

Function and Biological Significance

YWHAS is involved in several critical cellular functions:

• Cell Cycle Regulation: YWHAS plays a significant role in controlling the cell cycle by interacting with key regulators such as p53 and cdc25C. It helps maintain G2/M arrest following DNA damage, allowing for repair and preventing the propagation of damaged DNA.
• Apoptosis: It modulates apoptosis by binding to pro-apoptotic proteins, influencing the balance between cell survival and death.
• Tumor Suppression: YWHAS is considered a tumor suppressor protein, often downregulated in various cancers. It inhibits cell proliferation and promotes cell cycle arrest in response to DNA damage.
• Stress Response: YWHAS is involved in the cellular stress response, helping cells cope with oxidative stress and DNA damage by modulating relevant signaling pathways.
• Epithelial Cell Function: It is particularly important in epithelial cells, contributing to the maintenance of epithelial integrity and function.

Clinical Issues

Alterations in YWHAS expression or function are associated with several diseases:

• Cancer: YWHAS is frequently downregulated or silenced in various cancers, including breast, prostate, and lung cancers. Its loss can lead to uncontrolled cell proliferation and resistance to apoptosis, contributing to tumor progression.
• Neurodegenerative Disorders: While less studied than other 14-3-3 isoforms, dysregulation of YWHAS may also play a role in neurodegenerative diseases by affecting neuronal survival and function.
• Developmental Disorders: Mutations or dysregulation of YWHAS are associated with developmental disorders, particularly those involving abnormal cell cycle control and apoptosis.

Summary

YWHAS (14-3-3 protein sigma) is a multifunctional adaptor protein involved in essential cellular processes, including cell cycle regulation, apoptosis, tumor suppression, and stress response. Its conserved structure, featuring nine alpha helices and a phosphoserine/threonine-binding groove, enables it to interact with a wide range of phosphorylated target proteins. Dysregulation of YWHAS is linked to various diseases, particularly cancer, where it acts as a tumor suppressor. Understanding the molecular mechanisms and interactions of YWHAS can provide valuable insights into potential therapeutic targets for these diseases.