Dynamic modulation and posttranslational 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.

Apical-basal polarization is essential for epithelial tissue formation, segregating cortical domains to perform distinct physiological functions. Cortical lipid asymmetry has emerged as a determinant of cell polarization. We report a network of phosphatidylinositol phosphate (PIP)-modifying enzymes, some of which are transcriptionally induced upon embedding epithelial cells in extracellular matrix, and that are essential for apical-basal polarization. Unexpectedly, we find that PI(3,4)P2 localization and function is distinct from the basolateral determinant PI(3,4,5)P3. PI(3,4)P2 localizes to the apical surface, and Rab11a-positive apical recycling endosomes. PI(3,4)P2 is produced by the 5-phosphatase SHIP1 and Class-II PI3-Kinases to recruit the endocytic regulatory protein SNX9 to basolateral domains that are being remodeled into apical surfaces. Perturbing PI(3,4)P2 levels results in defective polarization through subcortical retention of apically destined vesicles at apical membrane initiation sites. We conclude that PI(3,4)P2 is a determinant of apical membrane identity.