TY - JOUR TI - Post-translational modifications on the K2 domain modulate SOX9 transcriptional activity in lung cancer DO - https://doi.org/doi:10.7282/t3-jgr0-nt90 PY - 2019 AB - Lung cancer is the deadliest cancer type, accounting for about 25% of all cancer-related deaths. Despite impressive advancements in the molecular characterization of lung cancer, more than 70% of lung cancer patients are still left with either no known clinically relevant driver mutation or with mutations for which there isn’t a targeted therapeutic option available. Thus, there is a great need to understand the underlying biology of this disease and to discover the molecular pathways driving its onset and progression. SOX9 is a transcription factor involved in several processes during embryonic development, and its role in promoting cancer-related features in lung cancer has been established. Here, we characterized the role of post-translational modifications in mediating SOX9-associated functions in the context of lung cancer, with a particular focus on modifications occurring on the K2 domain. We demonstrated that the K2 domain is able to modulate SOX9 transcriptional ability and that changes in the phosphorylation status of specific residues within K2 affect this mechanism. We were able to show that the K2 domain might represent a region of intrinsic disorder within SOX9, and that post-translational modifications are involved in the maintenance of this disorder, potentially resulting in the modulation of SOX9 ability to interact with binding partners. These results uncover the prominent role of the K2 domain in mediating specific SOX9 functions, thus contributing to dissect the mechanistic details of SOX9 impact on lung cancer onset and progression. KW - Pharmacology, Cellular and Molecular KW - Lungs -- Cancer -- Molecular aspects LA - English ER -