YWHAZ - 14-3-3 protein zeta/delta| Elisa - Clia - Antibody - Protein

Background

YWHAZ, also known as 14-3-3 protein zeta/delta, is a member of the highly conserved 14-3-3 protein family, which plays a crucial role in various cellular processes. These proteins function as adaptors or scaffold proteins, facilitating protein-protein interactions by binding to phosphorylated serine/threonine residues on target proteins. The 14-3-3 proteins are involved in the regulation of numerous cellular pathways, including signal transduction, cell cycle control, apoptosis, and cellular stress responses. YWHAZ, specifically, is expressed ubiquitously and is implicated in essential functions such as neuronal development, synaptic plasticity, and the regulation of the cytoskeleton. Dysregulation of YWHAZ has been associated with several diseases, including cancer, neurological disorders, and metabolic conditions, highlighting its significance in maintaining cellular homeostasis and proper physiological functions.

Protein Structure

YWHAZ is characterized by a highly conserved structure typical of 14-3-3 proteins, which includes:

• Alpha-helical structure: The protein forms a dimer, with each monomer consisting of nine alpha helices.
• Phosphoserine/threonine-binding groove: This groove allows YWHAZ to bind to specific phosphorylated motifs on target proteins, facilitating protein-protein interactions.
• Amphipathic binding sites: These sites contribute to the versatility of 14-3-3 proteins in binding diverse target proteins, thereby participating in various signaling pathways.

Classification and Subtypes

YWHAZ belongs to the 14-3-3 protein family, which comprises seven isoforms in mammals: β, γ, ε, η, σ, τ, and ζ/δ (YWHAZ). Each isoform has specific and overlapping functions, contributing to a wide range of cellular processes. YWHAZ, also known as 14-3-3ζ, is closely related to the δ isoform and is sometimes referred to as 14-3-3ζ/δ.

Function and Biological Significance

YWHAZ is involved in several critical cellular functions:

• Signal Transduction: By binding to phosphorylated proteins, YWHAZ modulates various signaling pathways, including those regulated by kinases such as RAF1 and PI3K.
• Cell Cycle Regulation: YWHAZ plays a role in controlling the cell cycle by interacting with cell cycle regulators like CDC25 and cyclin-dependent kinases.
• Apoptosis: YWHAZ can influence apoptosis by binding to pro-apoptotic factors like BAD, thereby regulating cell survival.
• Neuronal Development: In the nervous system, YWHAZ is involved in neuronal differentiation, synaptic plasticity, and memory formation.
• Cytoskeletal Regulation: YWHAZ interacts with cytoskeletal proteins, influencing cell morphology and motility.

Clinical Issues

Dysregulation of YWHAZ is associated with several pathological conditions:

• Cancer: Overexpression or altered function of YWHAZ has been linked to various cancers, including breast cancer, glioblastoma, and lung cancer. YWHAZ can promote tumor growth and metastasis by modulating signaling pathways that control cell proliferation and survival.
• Neurological Disorders: YWHAZ dysregulation is implicated in neurodegenerative diseases like Alzheimer's disease and Parkinson's disease, where it affects neuronal survival and synaptic function.
• Metabolic Disorders: Abnormal YWHAZ function is also associated with metabolic conditions such as diabetes, where it influences insulin signaling pathways and glucose metabolism.

Summary

YWHAZ (14-3-3 protein zeta/delta) is a vital adaptor protein involved in numerous cellular processes, including signal transduction, cell cycle regulation, apoptosis, neuronal development, and cytoskeletal organization. Its structure, featuring a conserved alpha-helical fold and phosphoserine/threonine-binding groove, allows it to interact with a wide range of phosphorylated target proteins. Dysregulation of YWHAZ is linked to various diseases, including cancer, neurological disorders, and metabolic conditions, highlighting its importance in maintaining cellular homeostasis. Understanding the molecular mechanisms of YWHAZ can provide insights into potential therapeutic targets for these diseases.