Abstract- Dynamic modulation and post-translational modification of proteins are tightly controlled biological processes
that occur in response to physiological cues. One such dynamic modulation is ubiquitination, which marks
proteins for degradation via the proteasome, altering their localization, affecting their activity, and promoting or
interfering with protein interactions. Hence, ubiquitination is crucial for a plethora of physiological processes,
including cell survival, differentiation and innate and adaptive immunity. Similar to kinases, components of the
ubiquitination system are often deregulated, leading to a variety of diseases, such as cancer and neurodegenerative
disorders. In a context-dependent manner, ubiquitination can regulate both tumor-suppressing and
tumor-promoting pathways in cancer. This review outlines how components of the ubiquitination systems (e.g.
E3 ligases and deubiquitinases) act as oncogenes or tumor suppressors according to the nature of their substrates.
Furthermore, I interrogate how the current knowledge of the differential roles of ubiquitination in cancer lead to
technical advances to inhibit or reactivate the components of the ubiquitination system accordingly.
