Sandbox 465

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Structure

To carry out enzymatic activities, STK11 forms a heterotrimeric complex with STE20-related adaptor (STRAD) and mouse protein 25 (MO25). STRAD, a pseudokinase, induces a conformational change of STK11 into its catalytically active state and transports STK11 from the nucleus to the cytoplasm. MO25, a scaffold protein, strengthens the binding of STK11 and STRAD, and as a result enhances STRAD’s effect on STK11’s kinase activity.

Location

The STK11 gene is located on chromosome 19 on the p arm of the chromosome, also known as the short arm. The exact location is between base pair 1,205,799 and 1,228,435. Location is found in both the nucleus and the cytoplasm. In humans, when STK11 is over express it is mostly located in the nucleus, having limited portions in the cytoplasm. When a cell is undergoing apoptosis, STK11 is found to translocate to the mitochondria. STK11 is mostly expressed in the seminiferous tubules of the testes, showing higher expression in the fetal tissues than in adult tissues.

Function

Serine/Threonine-protein kinase (STK11) is a tumor suppressor that plays a role in cell metabolism, cell polarity, apoptosis and DNA damage response. STK11 controls the activity or the AMP-activated protein kinase (AMPK) family members as well as other non AMPK family members. This enzyme acts by phosphorylating the T-loop of AMPK and non AMPK members.The non AMPK family proteins that it phosphorylates are STRADA, PTEN and possibly p53/TP53. While the AMPK members it phosphorylates are PRKAA1, PRKAA2, BRSK1, BRSK2, MARK1, MARK2 and others but not MELK. STK11 acts as a upstream regulator by mediating phosphorylation and activation of the AMPK catalytic subunits PRKAA1 and PRKAA2. It also regulates activation of autophagy when cells undergo nutrient deprivation, B-cell differentiation in the germinal center in response to DNA damage and inhibition of signaling pathway that promotes cell growth and proliferation when energy levels are low. Its inhibition of PI3K/Akt signaling activity in vein endothelial cells induces apoptosis in response to the oxidant peroxynitrite (in vitro). This enzyme also regulates UV-radiation induced DNA damage response and cell polarity by remodeling the actin cytoskeleton.

Disease

The function of the STK11 is to suppress tumors. A mutation in this protein increases the risk of cancer and carcinomas, cancer arising from the epithelial tissue of internal organs primarily in the gastrointestinal (GI) tract. The risk of cancer and carcinomas not only increases with mutation, but is influenced by old age as well. In addition to cancer, a germline mutation of STK11 also increases the chances of Peutz-Jeghers syndrome, an autosomal genetic dominant mutation characterized by the growth of hamartomatous polyps in the GI tract, neoplasm, and discoloration of the skin and mouth. Polyps are masses of tissues that arise in the bowl and penetrates the lumen, which can be removed though endoscopic technology. Neoplasm is abnormal growth of tissues that can be categorized into four categories- benign, institu, malignant, and unknown.

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