STK11: Difference between revisions

Serine-threonine kinase 11 (STK11) is a tumor suppressor gene that plays an important role in regulating cell growth, cell polarity, and apoptosis.  It controls the activity of adenine monophosphate-activated protein kinase ([[AMPK]]). STK11 is regulated by the pseudokinase STE20-related adaptor alpha (STRADA) and the protein mouse protein 25 (MO25). Both STRADA and MO25 allosterically promote the activation of STK11. In addition to activating STK11, MO25 stabilizes STK11 though interacting with the activation loop. The alpha helix is rotated into a closed conformation, conserving salt bridge between <scene name='72/728131/Lys/2'>lys78</scene> and <scene name='72/728131/Glu/3'>glu98</scene>. This is where the active conformation is formed <ref> PMID: 19892943 </ref>. STK11 facilitates cell cycle arrest through induction of a cyclin-dependent kinase inhibitor, p21WAF1, through a p53-dependent process to prevent cancer formation <ref name="loss"> PMID: 12861065</ref>. Cyclin-dependent kinase inhibitors like p21WAF1 function as a tumor suppressor gene that inhibits apoptosis and may promote cell proliferation in some tumors <ref> PMID: 19449443 </ref>. The gene p21WAF1is also critical for regulating proper cell division. STK11 also interacts with brahma-related gene-1 ([[Brg1]]), an ATPase that is associated with SWI/SNF chromatin-remodeling complexes. Exogenous expression of brg1 is able to induce cell cycle arrest thus resulting in a loss of cell power of division and growth in a retinoblastoma-dependent fashion.  The tumor suppression function of STK11 lies within its ability to affect the cell cycle proliferation <ref name="loss" />.