HERC Ubiquitin Ligases in Cancer
© 2020 by the authors. ; HERC proteins are ubiquitin E3 ligases of the HECT family. The HERC subfamily is composed of six members classified by size into large (HERC1 and HERC2) and small (HERC3–HERC6). HERC family ubiquitin ligases regulate important cellular processes, such as neurodevelopment, DNA damage response, cell proliferation, cell migration, and immune responses. Accumulating evidence also shows that this family plays critical roles in cancer. In this review, we provide an integrated view of the role of these ligases in cancer, highlighting their bivalent functions as either oncogenes or tumor suppressors, depending on the tumor type. We include a discussion of both the molecular mechanisms involved and the potential therapeutic strategies. ; J.L.R. is supported by the Spanish Ministry of Science and Innovation (BFU2016-80295-R, SAF2017-90900-REDT, and UBIRed). X.R.B. is supported by grants from the Castilla-León Government (CSI252P18, CLC-2017-01), the Spanish Ministry of Science and Innovation (SAF2015-64556-R, RTI2018-096481-B-100) and the Spanish Association against Cancer (GC16173472GARC). X.R.B.'s institution is supported by the Programa de Apoyo a Planes Estratégicos de Investigación de Estructuras de Investigación de Excelencia of the Castilla-León autonomous government (CLC-2017-01). Both Spanish and Castilla-León government-associated funding is partially supported by the European Regional Development Fund. J.S.-G. and A.M.-M. received FPU Fellowships (FPU17/02413 and FPU18/06325, respectively) from the Spanish Ministry of Science, Innovation and Universities.