Truncating PREX2 Mutations Activate Its GEF Activity and Alter Gene
Truncating PREX2 mutations activate its GEF activity PNAS PLUS and alter gene expression regulation in NRAS-mutant melanoma Yonathan Lissanu Deribea,1,2, Yanxia Shia,b,1, Kunal Raia, Luigi Nezia, Samir B. Amina, Chia-Chin Wua, Kadir C. Akdemira, Mozhdeh Mahdavia, Qian Penga, Qing Edward Changc, Kirsti Hornigoldd, Stefan T. Arolde, Heidi C. E. Welchd, Levi A. Garrawayf,g, and Lynda China,c,2 aDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030; bSun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborate Center for Cancer Medicine, Guangzhou 510060, China; cInstitute for Applied Cancer Science (IACS), The University of Texas MD Anderson Cancer Center, Houston, TX 77030; dThe Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, United Kingdom; eDivision of Biological and Environmental Sciences and Engineering, King Abdullah University of Science and Technology, Thuwal, 23955-6900 Saudi Arabia; fDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215; and gBroad Institute of MIT and Harvard, Boston, MA 02141 Edited by Dennis A. Carson, University of California at San Diego, La Jolla, CA, and approved January 26, 2016 (received for review July 14, 2015) PREX2 (phosphatidylinositol-3,4,5-triphosphate-dependent Rac- To date, the most obvious connection between PREX2 and exchange factor 2) is a PTEN (phosphatase and tensin homolog cancer relevant pathways is through its physical interaction with deleted on chromosome 10) binding protein that is significantly PTEN (7). PTEN catalyzes the conversion of phosphatidylino- mutated in cutaneous melanoma and pancreatic ductal adenocar- sitol-3,4,5-trisphosphate to phosphatidylinositol-4,5 bisphosphate.
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