Since the<unk> -STAT<unk>  plays a major role in many fundamental processes, such as apoptosis and inflammation, dysfunctional proteins in the<unk>  may lead to a number of diseases. For example, alterations in<unk> -STAT<unk>  can result in cancer and diseases affecting the immune system, such as severe combined immunodeficiency disorder (SCID). Immune system-related diseases Psoriasis on the hands can be caused by faulty<unk> -STAT<unk> .<unk> 3 can be used for the<unk>  of IL-2, IL-4, IL-15 and IL-21 (as well as other cytokines); therefore patients with mutations in the<unk> 3 gene often experience issues affecting many aspects of the immune system. For example, non-functional<unk> 3 causes SCID, which results in patients having no NK cells, B cells or T cells, and this would make SCID individuals susceptible to infection. Mutations of the<unk> 5 protein, which can signal with<unk> 3, has been shown to result in autoimmune disorders. It has been suggested that patients with mutations in<unk> 1 and<unk> 2 are often more likely to develop infections from bacteria and viruses. Also,<unk> 4 mutations have been associated with rheumatoid arthritis, and<unk> 6 mutations are linked to asthma. Patients with a faulty<unk>  may also experience skin disorders. For example, non-functional cytokine receptors, and overexpression of<unk> 3 have both been associated with psoriasis (an autoimmune disease associated with red, flaky skin).<unk> 3 plays an important role in psoriasis, as<unk> 3 can control the production of IL-23 receptors, and IL-23 can help the development of Th17 cells, and Th17 cells can induce psoriasis. Also, since many cytokines function through the<unk> 3 transcription factor,<unk> 3 plays a significant role in maintaining skin immunity. In addition, because patients with<unk> 3 gene mutations have no functional T cells, B cells or NK cells, they would more likely to develop skin infections. Cancer Cancer involves abnormal and uncontrollable cell growth in a part of the body. Therefore, since<unk> -STAT<unk>  can allow the transcription of genes involved in cell division, one potential effect of excessive<unk> -STAT<unk>  is cancer formation. High levels of<unk>  activation have been associated with cancer; in particular, high amounts of<unk> 3 and<unk> 5 activation is mostly linked to more dangerous tumours. For example, too much<unk> 3 activity has been associated with increasing the likelihood of melanoma (skin cancer) returning after treatment and abnormally high levels of<unk> 5 activity have been linked to a greater probability of patient death from prostate cancer. Altered<unk> -STAT<unk>  can also be involved in developing breast cancer.<unk> -STAT<unk>  in mammary glands (located within breasts) can promote cell division and reduce cell apoptosis during pregnancy and puberty, and therefore if excessively activated, cancer can form. High<unk> 3 activity plays a major role in this process, as it can allow the transcription of genes such as BCL2 and c-Myc, which are involved in cell division. Mutations in<unk> 2 can lead to leukaemia and lymphoma. Specifically, mutations in exons 12, 13, 14 and 15 of the<unk> 2 gene are proposed to be a risk factor in developing lymphoma or leukemia. Additionally, mutated<unk> 3 and<unk> 5 can increase<unk> -STAT<unk>  in NK and T cells, which promotes very high proliferation of these cells, and increases the likelihood of developing leukaemia. Also, a<unk>  mediated by erythropoietin (EPO), which usually allows the development of red blood cells, may be altered in patients with leukemia. Treatments Since excessive<unk> -STAT<unk>  is responsible for some cancers and immune disorders,<unk>  inhibitors have been proposed as drugs for therapy. For instance, to treat some forms of leukaemia, targeting and inhibiting<unk> s could eliminate the effects of EPO<unk>  and perhaps prevent the development of leukaemia. One example of a<unk>  inhibitor drug is Ruxolitinib, which is used as a<unk> 2 inhibitor.<unk>  inhibitors are also being developed, and many of the inhibitors target<unk> 3. It has been reported that therapies which target<unk> 3 can improve the survival of patients with cancer. Another drug, called Tofacitinib, has been used for psoriasis and rheumatoid arthritis treatment, and has been recently approved for Crohn's Disease and Ulcerative Colitis treatment.
JAK-STAT signaling pathway
Hedgehog signaling pathway
Insulin signal transduction pathway
Lectin pathway
Purinergic signalling
Biological functions of nitric oxide
Winged-helix transcription factors
TP53-inducible glycolysis and apoptosis regulator