Essay On Implication Of JK-STAT - 1490 Words

Implications of JAK-STAT in disease So far, we have seen that this pathway is accountable for the transduction of extracellular stimulus into transcriptional factors that regulate several cellular functions. STATs are also known to exert additional functions such as affecting oxidative phosphorylation in mitochondria, regulating chromatin compliance and epigenetic markings in the nucleus and interacting with the microtubule components in the cytoplasm which are responsible for cellular motility (4). This pathway has been observed to play an integral role in the development of mammary gland, stem cells, lymphocytes, neuronal cells, eye cells, cardiomyocytes, adipocytes. Consequently, its dysregulation induces various diseases, including†¦show more content†¦STATs contribute significantly to cellular fate decisions of differentiating naà ¯ve T cells into regulatory and inflammatory T cells, lymphocyte development, and exercise control over the intensity and duration of inflammatory responses. STAT3 particularly is involved in the regulation of cell death, cell growth and in the transcription of inflammatory genes. This serves as the basis for its contribution to the development of chronic inflammatory diseases and neurodegenerative diseases (8). This pathway has been associated with several monogenic diseases like the ‘bubble boy’ syndrome (X-linked severe combined immunodeficiency). The extreme susceptibility to pathogens observed is caused by a lack of T and NK cells, which occurs due to loss of function variants of the common ÃŽ ³ chain signal transduction. A subset of SCID patients demonstrated mutations in Jak3 kinase specifying the non-redundant in vivo functions for any JAK/STAT component (9). After the initial discovery of JAK3-SCID, many Mendelian disorders were reported. Discoveries made in the past three decades help us to correlate loss of function STAT mutations with specific types of pathogens. STAT1 mutations make patients vulnerable to viral and mycobacterial infections, whereas patients having STAT2 mutations are prone to viral infections and fungal infections are most common in patients with STAT3 mutations (2). The last 20 years have brought to the fore remarkable connections between JAK-STAT