PKM and colorectal cancer: The importance of non-proteolytic ubiquitylation in the metabolic reprogramming of tumor cells has also been confirmed by another recent study which reported a role for the DUB OTUB2 in promoting colorectal cancer progression by elevating the Pyruvate kinase M2 (PKM2) enzymatic activity, subsequently upregulating glycolysis139 Upon conditions of nutrient deficiency, OTUB2 co-localizes and interacts with PKM2 in the cytoplasm and blocks its ubiquitylation.