Chapters authored
Ubiquitin Signaling in Regulation of the Start of the Cell Cycle
The small protein ubiquitin plays a vital role in virtually all aspects of cellular life. Among the diverse signaling outcomes associated with ubiquitination, the most well-established is the targeted degradation of substrates via the proteasome. During cell growth and proliferation, ubiquitin plays an outsized role in promoting progression through the cell cycle. In particular, ubiquitin-mediated degradation is critically important at transition points where it provides directionality and irreversibility to the cell cycle, which is essential for maintaining genome integrity. Specifically, the boundary between G1 and S-phase is tightly regulated by the ubiquitin proteasome system. Notably, the G1/S boundary represents a major barrier to cell proliferation and is universally dysfunctional in cancer cells, allowing for the unbridled proliferation observed in malignancy. Numerous E3 ubiquitin ligases, which facilitate the ubiquitination of specific substrates, have been shown to control G1/S. In this chapter, we will discuss components in the ubiquitin proteasome system that are implicated in G1/S control, how these enzymes are interconnected, gaps in our current knowledge, and the potential role of these pathways in the cancer cycle and disease proliferation.
Part of the book: Ubiquitin Proteasome System