User:Peyton Jenkins/Sandbox 1

Relevance and Disease

Lung cancer is the leading cause of cancer related death worldwide. In the United States alone, over 120,000 deaths were caused by lung cancer in 2024^[1]. Non small cell lung cancer make up approximately 84% of all lung cancer cases, and of these lung adenocarcinoma accounts for about 65%^[2]. In lung adenocarcinoma, STK11 is the third most commonly mutated gene, behind only KRAS and p53^[3]. STK11 is a master kinase, signalling upstream of AMPK family kinases, p53, and FAK, to regulate processes like anoikis, adhesion, growth, metabolism, and survival^{[4], [5]}. STK11 exists in a heterotrimeric complex with the pseudokinase STRADα, and the scaffolding protein MO25. This complex is essential for both proper kinase activity and proper localization. ^{[6], [7]}

Structural Highlights

STK11

STK11 can be broken down into 3 domains. An N-terminal domain (aa 1-42), kinase domain (aa 43-347), and a C-terminal domain (aa 348-433). The activation loop of STK11 is located from residues ~202-212. Within the activation loop is P204, which interacts with a hydrophobic pocket on MO25, which is necessary to stabilize the active conformation.

STRADα

The WEF motif (aa 429-431) on the C-terminus of STRADα with the C-terminus of MO25 interacts .

References

1. ↑ https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2024/2024-cancer-facts-and-figures-acs.pdf
2. ↑ 10.1001/jamaoncol.2021.4932
3. ↑ 10.1091/mbc.E15-08-0569.
4. ↑ 10.1038/sj.emboj.7600110
5. ↑ 10.1074/jbc.M112.444620
6. ↑ 10.1038/sj.emboj.7600110
7. ↑ 10.1093/emboj/cdg490