YWHAQ - 14-3-3 protein theta | Elisa - Clia - Antibody - Protein

Background

YWHAQ, also known as 14-3-3 protein theta, is a member of the 14-3-3 family of proteins, which are highly conserved across eukaryotic species and play critical roles in a variety of cellular processes. These proteins act as molecular scaffolds, facilitating protein-protein interactions by binding to phosphorylated serine/threonine residues on target proteins. YWHAQ is involved in numerous cellular functions, including signal transduction, cell cycle control, apoptosis, and response to stress. It is particularly significant in the brain, where it contributes to neuronal development, synaptic plasticity, and memory formation. Alterations in YWHAQ expression or function can lead to various diseases, including cancers and neurodegenerative disorders, making it an important target for therapeutic research.

Protein Structure

The structure of YWHAQ, like other 14-3-3 proteins, is characterized by:

• Alpha-helical Composition: YWHAQ monomers are composed of nine alpha helices, which are arranged in a highly conserved fashion.
• Dimerization: Functional YWHAQ typically forms dimers, which are essential for its activity. The dimeric structure allows the protein to interact simultaneously with multiple target proteins.
• Phosphoserine/Threonine-binding Groove: The dimerization creates a central binding groove that accommodates phosphorylated serine/threonine residues on target proteins.
• Flexible Binding Sites: These sites enable YWHAQ to interact with a diverse array of proteins, facilitating its role in various signaling pathways and cellular processes.

Classification and Subtypes

YWHAQ is one of the seven mammalian isoforms of the 14-3-3 protein family, which includes β, γ, ε, η, σ, τ, and ζ. Each isoform has unique as well as overlapping functions in different tissues and cellular contexts, contributing to the diversity of the 14-3-3 protein family's roles in cellular regulation.

Function and Biological Significance

YWHAQ is involved in several critical cellular functions:

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

Clinical Issues

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

• Cancer: Dysregulation of YWHAQ has been implicated in various cancers, including breast cancer, lung cancer, and gliomas. It can affect tumor progression by influencing cell proliferation and survival pathways.
• Neurodegenerative Disorders: YWHAQ is associated with neurodegenerative diseases such as Alzheimer's and Parkinson's disease, where it impacts neuronal survival and function.
• Developmental Disorders: Mutations or dysregulation of YWHAQ are associated with developmental disorders, particularly those involving brain malformations and cognitive impairments.

Summary

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