YWHAH - 14-3-3 protein eta | Elisa - Clia - Antibody - Protein

Background

YWHAH, also known as 14-3-3 protein eta, is a member of the highly conserved 14-3-3 protein family that plays a pivotal role in regulating numerous cellular processes. These proteins function primarily as adaptors or scaffolds, facilitating protein-protein interactions by binding to phosphorylated serine/threonine residues on target proteins. YWHAH is ubiquitously expressed across various tissues and is involved in critical functions such as signal transduction, cell cycle control, apoptosis, and stress response. It is particularly significant in the nervous system, where it influences neuronal development and synaptic plasticity. Dysregulation of YWHAH has been implicated in a range of diseases, including cancer, neurodegenerative disorders, and developmental abnormalities, making it a crucial protein for maintaining cellular homeostasis and proper physiological function.

Protein Structure

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

• Alpha-helical composition: Each monomer consists of nine alpha helices that form a stable dimer.
• Dimerization: The dimeric form is essential for its functional activity, allowing it to interact with multiple target proteins simultaneously.
• Binding Groove: The central binding groove formed by the dimer allows YWHAH to bind phosphorylated serine/threonine motifs on target proteins.
• Versatile Binding Sites: These sites enable YWHAH to interact with a wide array of proteins, facilitating its involvement in various signaling pathways and cellular processes.

Classification and Subtypes

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

Function and Biological Significance

YWHAH is involved in several key cellular functions:

• Signal Transduction: YWHAH modulates various signaling pathways by binding to phosphorylated proteins, influencing processes such as cell growth, differentiation, and apoptosis.
• Cell Cycle Regulation: It interacts with cell cycle regulators, including Cdc25 phosphatases and cyclin-dependent kinases (CDKs), ensuring proper cell division and growth.
• Apoptosis: By binding to pro-apoptotic proteins like BAD and Bax, YWHAH regulates apoptosis and promotes cell survival.
• Neuronal Development: In the nervous system, YWHAH is involved in neuronal differentiation, synaptic plasticity, and memory formation.
• Stress Response: YWHAH 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 YWHAH expression or function are associated with several diseases:

• Cancer: Dysregulation of YWHAH has been linked to various cancers, including breast cancer, lung cancer, and gliomas. It can influence tumor progression by affecting cell proliferation and survival pathways.
• Neurodegenerative Disorders: YWHAH is implicated in neurodegenerative diseases like Alzheimer's and Parkinson's disease, where it affects neuronal survival and function.
• Developmental Disorders: Mutations or dysregulation of YWHAH are associated with developmental disorders, including those involving brain malformations.
• Psychiatric Disorders: YWHAH has been implicated in psychiatric conditions such as schizophrenia and bipolar disorder, likely due to its role in neural signaling and plasticity.

Summary

YWHAH (14-3-3 protein eta) is a multifunctional adaptor protein involved in critical cellular processes, including signal transduction, cell cycle regulation, apoptosis, and stress response. Its 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 YWHAH is linked to various diseases, including cancer, neurodegenerative disorders, and developmental conditions, underscoring its importance in maintaining cellular homeostasis. Understanding the molecular mechanisms and interactions of YWHAH can provide insights into potential therapeutic targets for these diseases.