KRT8 - Keratin 8 (Cytokeratin 8) | Elisa - Clia - Antibody - Protein

Background:

Keratin 8 (KRT8) is a type II intermediate filament protein that is part of the keratin family, which comprises the structural proteins found in epithelial cells. KRT8 is a cytoskeletal protein that forms heterodimers with keratin 18 (KRT18). These heterodimers assemble into intermediate filaments, which are structural components of the cytoskeleton. Intermediate filaments provide mechanical support and stability to cells, particularly epithelial cells, and play a role in cell shape, migration, and resistance to mechanical stress.KRT8 is expressed in a variety of epithelial tissues throughout the body, including the liver, kidney, pancreas, gastrointestinal tract, respiratory tract, and reproductive organs. It is particularly abundant in simple epithelia, such as the single-layered epithelium lining the interior surface of organs. KRT8, along with KRT18, forms intermediate filaments that provide mechanical support and integrity to epithelial cells. These filaments help maintain cell shape and resist mechanical stress, such as stretching and compression. Epithelial tissues, where KRT8 is abundant, serve as protective barriers against physical, chemical, and microbial insults. The cytoskeletal network formed by KRT8 contributes to the strength and resilience of these epithelial barriers. KRT8 has been implicated in the regulation of cell signaling pathways and apoptosis (programmed cell death). It interacts with various signaling molecules and cytoskeletal proteins, influencing cellular processes such as cell adhesion, migration, and survival. Mutations or dysregulation of KRT8 expression have been associated with several diseases, including liver disease, pancreatic cancer, inflammatory bowel disease, and certain types of tumors. Changes in KRT8 expression levels or distribution patterns may serve as diagnostic markers or indicators of disease progression.

Protein Structure:

KRT8, like other keratins, consists of three main domains:

• Central Alpha-Helical Rod Domain: This domain enables the formation of coiled-coil dimers with type I keratins, particularly KRT18. The rod domain is critical for the assembly and stability of intermediate filaments.
• Non-Helical Head and Tail Domains: These terminal regions are involved in regulating filament assembly, interaction with other cellular components, and undergoing post-translational modifications.

Classification and Subtypes:

Keratin proteins are classified into two main types:

• Type I (Acidic) Keratins: Includes KRT18 and other acidic keratins.
• Type II (Basic/Neutral) Keratins: Includes KRT8, which pairs with type I keratins to form intermediate filaments.

Function and Biological Significance:

KRT8, in combination with KRT18, performs several critical functions:

• Structural Support: Provides mechanical stability to epithelial cells, helping them resist shear stress and maintain integrity.
• Cell Signaling: Participates in various signaling pathways that influence cell growth, differentiation, and apoptosis.
• Apoptosis and Stress Response: During cell stress and apoptosis, KRT8 undergoes specific modifications and cleavage, serving as a marker for these processes.
• Tissue Repair: Plays a role in wound healing and regeneration of epithelial tissues.

Interactions:

• KRT18: Forms stable heterodimers with KRT18, essential for the assembly of intermediate filaments in simple epithelial cells.
• Other Cytoskeletal Proteins: Interacts with actin, microtubules, and other cytoskeletal components, contributing to the overall cytoskeletal network.
• Signaling Molecules: Binds to proteins such as 14-3-3, influencing various signaling pathways involved in cell cycle regulation and apoptosis.

Clinical Issues:

• Cancer: KRT8 expression is frequently altered in various epithelial cancers, including liver, colorectal, and breast cancers. It serves as a diagnostic and prognostic marker in these cancers. Its role in apoptosis and cell stress responses makes it a potential therapeutic target.
• Liver Diseases: Increased levels of KRT8 fragments in the blood are associated with liver injury and can be used as biomarkers for liver diseases such as hepatitis, cirrhosis, and liver fibrosis.
• Genetic Disorders: Mutations in the KRT8 gene can cause or contribute to certain genetic disorders affecting epithelial tissues, although such mutations are relatively rare.

Summary:

KRT8 is a vital type II intermediate filament protein in simple epithelial cells, providing structural support and participating in essential cellular functions, including cell signaling and apoptosis. Its interaction with KRT18 forms a crucial part of the cytoskeletal framework. Clinically, KRT8 is significant as a biomarker for liver diseases and various cancers, offering insights into disease diagnosis, prognosis, and potential therapeutic targets. Research continues to uncover the diverse roles of KRT8 in health and disease, emphasizing its importance in cellular biology.