User:Raechu02/Type I keratin/Bibliography

Type I keratins are a class of structural proteins that belong to the larger keratin protein family. Keratins are intermediate filament-forming proteins, and they are a vital component of the cytoskeleton in epithelial cells. It has been studied extensively when mutations disrupt the genetic blueprint regulating Type I keratin production, since it can lead to a plethora of disorders collectively known as keratinopathies.

Structure
The structure of Type I keratins is characterized by a central alpha-helical rod domain enclosed by non-helical head and tail domains. Their unique composition is determined by genetic code and features a significant sequence of amino acids. These rod domains are essential for the assembly of keratins into heterodimers, which further associate to form intermediate filaments. This arrangement allows for the formation of a coiled-coil pattern. Crucial to this structure is the involvement of a specific amino acid, cysteine, which plays a important role in the production of disulfide bonds. These bonds contribute to the stability of the coiled-coil structure, making it more durable. In some cases, Type I keratins join forces with Type II keratins to form pairs, making the structure more stable. Moreover, Type I keratins are susceptible to modifications, such as phosphorylation, which involves adding phosphate groups. These alterations serve to regulate the assembly and function of filaments.

Type I Keratin Disorders
Deviations in Type I keratin expression are the product of the advancement of certain cancers. Aberrant expression of specific keratins is observed in various epithelial cancers, serving as potential indicators. Understanding the molecular pathways in these associations opens avenues for targeted therapeutic treatment of cancers. The connection between Type I keratin mutations and Epidermolysis Bullosa Simplex (EBS) emphasizes the contribution of these proteins to the composition of the skin. The cytoskeleton provided by keratin intermediate filaments is crucial for withstanding physical stress, and any deviations from the normal structure can lead to debilitating consequences for those affected. Therefore, EBS exemplifies the essential role of Type I keratins in the equilibrium of epithelial tissues.

Looking beyond genetic anomalies, variations in Type I keratin expression have been observed in the progression of certain cancers. The abnormal expression of specific keratins seen in epithelial cancers serves as potential diagnostic markers and therapeutic targets. Furthermore, the dynamics of Type I keratin expression in cancer cells reflect the heterogeneity of tumor types.

Uncommon expression patterns of Type I keratins have been identified in cancers affecting diverse tissues, including the breast, lung, pancreas, and bladder. In breast cancer, for instance, modifications in keratin expression can provide valuable information about the molecular subtypes of tumors and their prognosis. Certain keratins, such as K8 and K18, are linked with luminal subtypes of breast cancer, while K5 and K14 are more commonly expressed in basal-like subtypes.

The presence of keratins in circulating tumor cells and their potential as biomarkers in liquid biopsies is an area of active research. Detection and analysis of keratin levels in blood samples could offer non-invasive means for monitoring disease progression, evaluating treatment response, and predicting patient outcomes.

Evolution
The animal kingdom is bursting with a diverse array of keratin genes, showcasing the incredible adaptability and evolution of this essential protein. Within this genetic pool, Type I keratins work in tandem with their Type II counterparts to form intermediate filaments, each uniquely tailored to the demands of different tissues. This remarkable adaptability, borne from selective pressures, manifests in the various subtypes of keratins that exhibit tissue-specific expression patterns. Among mammals, the emergence of a diverse range of skin appendages, including hair, has been driven by the evolution of keratin expression. In fact, the development of hair is intricately linked to changes in keratin composition, serving vital purposes such as insulation, protection, and sensory functions. Beyond hair, the evolution of specialized skin glands, like sweat glands, is a testament to the remarkable versatility of keratins in fulfilling tissue-specific roles.