Carmen Paulmann, Ria Spallek, Oleksandra Karpiuk, Michael Heider, Isabell Schäffer, Jana Zecha, Susan Klaeger, Michaela Walzik, Rupert Öllinger, Thomas Engleitner, Matthias Wirth, Ulrich Keller, Jan Krönke, Martina Rudelius, Susanne Kossatz, Roland Rad, Bernhard Kuster, Florian Bassermann
Deubiquitylases (DUBs) are therapeutically amenable components of the ubiquitin machinery that stabilize substrate proteins. Their inhibition can destabilize oncoproteins that may otherwise be undruggable. Here, we screened for DUB vulnerabilities in multiple myeloma, an incurable malignancy with dependency on the ubiquitin proteasome system and identified OTUD6B as an oncogene that drives the G1/S-transition. LIN28B, a suppressor of microRNA biogenesis, is specified as a bona fide cell cycle-specific substrate of OTUD6B...
September 5, 2022: EMBO Journal