Tumor suppression by mitotic quality control (472.1)

Abstract

Posttranslational modification with ubiquitin, a reaction referred to as ubiquitylation, is essential for accurate cell division and differentiation in all eukaryotes, and accordingly, the aberrant regulation of ubiquitylation enzymes is one of the most frequent causes for tumorigenesis. Ubiquitylation enzymes synthesize different types of modifications, such as polymeric ubiquitin chains of distinct topology, and depending on the type of the ubiquitin mark, ubiquitylation can differentially regulate the activity, localization, or stability of critical cell cycle regulators. Unfortunately, most ubiquitylation enzymes have not been paired with their important substrates and the biological consequences of most ubiquitin marks remain poorly understood. As a consequence, powerful strategies to target ubiquitylation enzymes for therapeutic benefit have not been developed. Here, I will discuss recent progress in identifying new ubiquitylation enzymes and determining their functions in cell cycle control. Our findings have revealed an intriguing role for ubiquitylation in ensuring proper assembly of oligomeric complexes required for cell division, and accordingly, loss of the processes identified in this work can lead to tumorigenesis. Our work, therefore, identifies an important role for mitotic quality control in tumor suppression.