The SUMOylation inhibitor TAK-981 induces a transcriptional reprogramming in human Natural Killer cells [RNA-seq]

SUMOylation, a post-translational modification of the ubiquitin family plays a critical role in the regulation of proteins function and fate. TAK-981 (Subasumstat) is a first-in-class inhibitor of the SUMO-activating enzyme used in various phase I/II clinical trials for solid tumors and lymphomas. In addition to its direct cytotoxic effect on cancer cells, TAK-981 activates anti-tumor immune response. We show here that TAK-981 activates human natural killer cells. TAK-981 mostly regulates genes involved in inflammation and immune response, in particular those related to the type-I and type-II interferon pathway. Total RNA was purified from FACS-sorted NK cells (CD56+/CD3-) sorted from 3 different healthy donors' blood treated with mock or 100 nM TAK-981 for 24 h.