YWHAE - 14-3-3 protein epsilon | Elisa - Clia - Antibody - Protein

Background:

YWHAE, also known as 14-3-3 protein epsilon, is a member of the 14-3-3 family of proteins, which are highly conserved and ubiquitously expressed in eukaryotic cells. These proteins act as molecular adaptors, playing a critical role in regulating various cellular processes by binding to phosphorylated serine/threonine residues on target proteins. YWHAE is involved in numerous cellular functions, including signal transduction, cell cycle control, apoptosis, and response to cellular stress. It is particularly important in the nervous system, where it influences neuronal development and function. The versatility of YWHAE in interacting with a wide range of proteins underpins its significance in maintaining cellular homeostasis and responding to external stimuli.

Protein Structure

YWHAE, like other 14-3-3 proteins, is characterized by the following structural features:

• Alpha-helical Structure: Each monomer consists of nine alpha helices, forming a rigid structure that is essential for its function.
• Dimerization: YWHAE typically functions as a dimer, which is crucial for its ability to bind and stabilize target proteins.
• Phosphoserine/Threonine-binding Groove: The central channel formed by the dimer allows YWHAE to bind to phosphorylated motifs on target proteins, facilitating protein-protein interactions.
• Flexible Binding Sites: These sites enable YWHAE to interact with a diverse range of target proteins, contributing to its involvement in various cellular processes.

Classification and Subtypes

The 14-3-3 protein family consists of seven isoforms in mammals: β, γ, ε, η, σ, τ, and ζ. YWHAE, specifically known as 14-3-3ε, is one of these isoforms and is involved in numerous regulatory processes across different tissues.

Function and Biological Significance

YWHAE performs several critical functions in the cell:

• Signal Transduction: YWHAE modulates various signaling pathways by binding to phosphorylated proteins, influencing processes such as cell growth, differentiation, and apoptosis.
• Cell Cycle Regulation: YWHAE interacts with cell cycle regulators like Cdc25 phosphatases and cyclin-dependent kinases (CDKs), ensuring proper cell division and growth.
• Apoptosis: By binding to pro-apoptotic proteins such as BAD and Bax, YWHAE regulates apoptosis and cell survival.
• Neuronal Development: In the nervous system, YWHAE is involved in neuronal differentiation, synaptic plasticity, and memory formation.
• Response to Stress: YWHAE plays a role in the cellular stress response, helping cells cope with oxidative stress and DNA damage by modulating relevant signaling pathways.

Clinical Issues

Alterations in YWHAE expression or function are linked to several diseases:

• Cancer: Overexpression or dysregulation of YWHAE has been associated with various cancers, including breast cancer, lung cancer, and gliomas. It can promote tumor growth and metastasis by affecting cell proliferation and survival pathways.
• Neurological Disorders: YWHAE is implicated in neurodegenerative diseases like Alzheimer's and Parkinson's disease, where it affects neuronal survival and function.
• Developmental Disorders: Mutations or deletions involving YWHAE are associated with developmental disorders, including Miller-Dieker syndrome and other conditions characterized by brain malformations.
• Cardiovascular Diseases: YWHAE's role in regulating apoptosis and cell survival also makes it relevant in the context of cardiovascular diseases, where it can influence heart function and response to ischemic damage.

Summary

YWHAE (14-3-3 protein epsilon) is a multifunctional adaptor protein involved in critical cellular processes, including signal transduction, cell cycle regulation, apoptosis, and stress response. Its structure, characterized by alpha helices and a phosphoserine/threonine-binding groove, enables it to interact with a wide range of target proteins. Dysregulation of YWHAE is linked to various diseases, including cancer, neurological disorders, and developmental conditions, underscoring its importance in maintaining cellular homeostasis. Understanding the molecular mechanisms and interactions of YWHAE can provide insights into potential therapeutic targets for these diseases.