KRT18 - Keratin 18 (Cytokeratin 18) | Elisa - Clia - Antibody - Protein

Background:

Keratin 18 (KRT18) is a type I intermediate filament protein that forms heterodimers with keratin 8 (KRT8), another type II keratin protein. Together, they comprise the intermediate filament network in epithelial cells, providing structural support and mechanical integrity. KRT18 is a cytoskeletal protein that belongs to the keratin family, which consists of intermediate filament proteins found in epithelial cells. It forms heterodimers with KRT8, and these heterodimers assemble into intermediate filaments through coiled-coil interactions. The assembly of KRT18 and KRT8 into intermediate filaments contributes to the cytoskeletal network that maintains the structural integrity of epithelial cells. KRT18 is expressed in a wide range of epithelial tissues throughout the body, including the liver, pancreas, gastrointestinal tract, respiratory tract, and reproductive organs. It is particularly abundant in simple epithelia, where it plays a key role in providing mechanical support and resilience to these tissues. KRT18, along with KRT8, forms intermediate filaments that provide mechanical strength and resilience to epithelial cells. These filaments help maintain cell shape, integrity, and resistance to mechanical stress, such as stretching and compression. Epithelial tissues, where KRT18 is abundant, serve as protective barriers against physical, chemical, and microbial insults. The cytoskeletal network formed by KRT18 contributes to the strength and integrity of these epithelial barriers, helping to prevent damage and maintain tissue homeostasis. KRT18 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 KRT18 expression have been associated with several diseases, including liver disease, pancreatic cancer, inflammatory bowel disease, and certain types of tumors. Changes in KRT18 expression levels or distribution patterns may serve as diagnostic markers or indicators of disease progression.

Protein Structure:

KRT18, like other keratins, is characterized by a central alpha-helical rod domain flanked by non-helical head and tail domains:

• Alpha-Helical Rod Domain: Facilitates the formation of coiled-coil dimers with KRT8, which then assemble into larger filamentous structures.
• Head and Tail Domains: These non-helical regions are involved in filament assembly, interaction with other proteins, and post-translational modifications.

Classification and Subtypes:

Keratins are classified into two types:

• Type I (Acidic) Keratins: Includes KRT18.
• Type II (Basic/Neutral) Keratins: Includes KRT8, the binding partner of KRT18.

Function and Biological Significance:

KRT18, together with KRT8, performs several vital functions:

• Structural Support: Provides mechanical stability to epithelial cells, maintaining cellular integrity and resistance to stress.
• Cell Signaling: Participates in various signaling pathways that regulate cell growth, apoptosis, and differentiation.
• Apoptosis: During apoptosis, KRT18 undergoes specific cleavage, which serves as a marker for cell death in epithelial tissues.

Interactions:

• KRT8: Forms heterodimers with KRT18, essential for the formation of intermediate filaments in simple epithelial cells.
• Other Cytoskeletal Proteins: Interacts with actin and microtubules, integrating various components of the cytoskeleton.
• Signaling Molecules: Engages with signaling proteins like 14-3-3 and certain kinases, influencing cell signaling pathways.

Clinical Issues:

• Liver Diseases: Elevated levels of KRT18 fragments in serum are biomarkers for liver cell apoptosis and necrosis, useful in diagnosing and monitoring liver diseases like hepatitis and liver fibrosis.
• Cancer: KRT18 is involved in tumor biology, and its expression patterns can serve as diagnostic markers for certain epithelial cancers, including breast, liver, and colorectal cancers. Its role in apoptosis also makes it a potential target for cancer therapy.
• Genetic Disorders: Mutations in KRT18 can lead to various genetic disorders affecting epithelial tissues, although such mutations are relatively rare.

Summary:

KRT18 is a crucial component of the cytoskeletal framework in simple epithelial cells, providing structural support and participating in essential cellular functions. Its interactions with KRT8 and other proteins facilitate a range of biological processes, including cell signaling and apoptosis. Clinically, KRT18 is significant as a biomarker for liver disease and certain cancers, and its involvement in cell death pathways offers potential therapeutic targets. Understanding KRT18's role in health and disease continues to be an important area of biomedical research.