Sandbox 465: Difference between revisions

Serine-threonine kinase (STK11) is a tumor suppressor gene that plays an important role in regulating cell growth, cell polarity and apoposis.  It controls the activity of adenine monophosphate-activated protein kinase (AMPK). STK11 is regulated by the pseudokinase STRADA and the protein MO25. Both STRADA and MO25 allosterically promote the activation of  STK11, which is also stabilized by MO25 interacting with the STK11 activation loop  . The STK11 alpha helix is rotated into a closed conformation, forming the consevered salt bridge between <scene name='72/728131/Lys/1'>lys78</scene> and <scene name='72/728131/Glu/2'>glu98</scene>. This is where the active conformation is formed <ref> PMID: 19892943</ref>. STK11 facilitates cell cycle arrest through induction of cyclin-dependent kinase inhibitor p21WAF1, through a p53-dependent process <ref name="loss"> PMID: 12861065 </ref>

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). This is due to improper DNA repair mechanisms and resistance to apoptosis which are both associated to an accumulation of cyclin-dependent kinase inhibitor 1A (CDKN1A). Therefore a mutation in SKT11 leads to CDKN1A malfunction. CDKN1A regulates cell development during the G1 and S phase of interphase and activates cyclin-dependent kinase2 to regulate apoptosis. <ref> PMID: 25329316 </ref>. In addition to cancer, a germline mutation of STK11 also increases the chances of Peutz-Jeghers (PJ) syndrome, an autosomal genetic dominant mutation caused by a disruption of the kinase domain function. PJ syndrome is characterized by the growth of hamartomatous polyps in the GI tract, neoplasm, and discoloration of the skin and mouth. <ref> PMID: 9425897 </ref>.