MAP4K1 and familial pancreatic carcinoma: In addition, Wang et al. revealed that the CUL7/Fbxw8 E3 ligase regulated the ubiquitination and targeted degradation of HPK1, which inhibited HPK1 activation and promoted pancreatic cancer cell proliferation, and the ubiquitination of HPK1 was mediated by its kinase activity in a phosphorylation-dependent manner23,102,103.