YWHAB - 14-3-3 protein beta/alpha| Elisa - Clia - Antibody - Protein

Background:

YWHAB, also known as 14-3-3 protein beta/alpha, is a member of the 14-3-3 family of proteins that are involved in a wide range of cellular processes through their role as adaptors, scaffolds, and regulators of signal transduction pathways. These proteins are highly conserved and ubiquitously expressed in eukaryotic cells. They function primarily by binding to phosphorylated serine/threonine residues on target proteins, which can affect the activity, localization, and stability of these targets. YWHAB, in particular, has been implicated in numerous critical cellular functions, including cell cycle regulation, apoptosis, stress response, and metabolic control. Due to its involvement in these essential pathways, YWHAB plays a significant role in maintaining cellular homeostasis and responding to external stimuli.

Protein Structure

YWHAB, like other 14-3-3 proteins, is characterized by a dimeric structure:

• Alpha-helical Composition: Each monomer consists of nine alpha helices that create a rigid structure capable of forming dimers.
• Dimerization: The dimerization of 14-3-3 proteins is crucial for their function, allowing them to interact with multiple partners simultaneously.
• Binding Groove: The central channel formed by the dimer serves as the binding groove for phosphoserine/threonine-containing motifs on target proteins.
• Flexible Binding Sites: These sites enable YWHAB to accommodate a wide variety of target proteins, thereby participating in diverse cellular processes.

Classification and Subtypes

The 14-3-3 protein family consists of seven isoforms in mammals, namely β (YWHAB), γ, ε, η, σ, τ, and ζ. Each isoform, while sharing a high degree of structural similarity, can have specific and overlapping functions in different tissues and cellular contexts. YWHAB, specifically, is often referred to as 14-3-3β and is known to be involved in a variety of regulatory processes.

Function and Biological Significance

YWHAB performs several key functions in the cell:

• Cell Cycle Control: YWHAB regulates the cell cycle by interacting with cell cycle-related proteins such as Cdc25 phosphatases and cyclin-dependent kinases (CDKs), ensuring proper cell division and growth.
• Apoptosis Regulation: By binding to pro-apoptotic proteins like BAD and Bax, YWHAB influences the apoptotic pathways and cell survival.
• Stress Response: YWHAB is involved in the cellular stress response, helping cells to cope with oxidative stress and DNA damage by modulating signaling pathways.
• Metabolic Regulation: It plays a role in metabolic processes by interacting with enzymes and other proteins involved in metabolism, thereby influencing glucose and lipid homeostasis.
• Signal Transduction: YWHAB modulates various signaling pathways, including those mediated by kinases such as Raf-1 and PI3K/Akt, affecting diverse cellular outcomes.

Clinical Issues

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

• Cancer: Overexpression or dysregulation of YWHAB has been associated with various cancers, including breast cancer, lung cancer, and gliomas. Its role in promoting cell proliferation and inhibiting apoptosis can contribute to tumor development and progression.
• Neurological Disorders: YWHAB is implicated in neurodegenerative diseases like Alzheimer's and Parkinson's disease, where it affects neuronal survival and synaptic function.
• Metabolic Diseases: Changes in YWHAB function can influence metabolic disorders such as diabetes, where it impacts insulin signaling and glucose metabolism.
• Cardiovascular Diseases: YWHAB's role in cell survival and stress responses also makes it relevant in the context of cardiovascular diseases, where it can affect heart function and response to ischemic damage.

Summary

YWHAB (14-3-3 protein beta/alpha) is a versatile adaptor protein involved in numerous cellular processes, including cell cycle regulation, apoptosis, stress response, and metabolism. Its dimeric structure and binding groove allow it to interact with a wide range of phosphorylated target proteins, facilitating its role in signal transduction. Dysregulation of YWHAB is linked to various diseases, including cancer, neurological disorders, and metabolic conditions, highlighting its importance in maintaining cellular homeostasis. Understanding the molecular mechanisms and interactions of YWHAB can provide insights into potential therapeutic targets for these diseases.