Serine/threonine-specific protein phosphatases and cancer

Abstract

In a multicellular organism, the cell number depends on the balance between cell proliferation and programmed cell death or apoptosis. Human cancer is a disease that involves unrestrained cell cycle progression and/or a failure to undergo apoptosis. While we have identified the essential pathways controlling the cell number, we have realised that these two processes are regulated by protein phosphorylation/dephosphorylation. Considerable effort is now being devoted towards testing and exploiting molecular targets that can improve the mostly frustrating results of present chemotherapy. Given that our understanding of protein phosphorylation is far better than that of protein dephosphorylation, it is not surprising that most of the work is currently focused on select protein kinases, their regulators and substrates. This review will discuss recent advances in the characterisation of protein phosphatases, which play a role in controlling the cell number and, at the same time, attempt to identify important areas for future research. While protein kinases in general function as positive regulators of cell cycle progression and cell survival, most, but not all, protein phosphatases have been shown to have the opposite effect. Several phosphatases decelerate or block cell cycle progression and/or facilitate cell death. Collectively, these findings raise the possibility that protein phosphatases are novel targets for significantly improved therapy of cancer. Specific approaches to exploit this potential will be discussed.

• apoptosis
• cancer
• Cdk
• cell cycle
• cell survival
• checkpoint control
• cyclin
• drug target
• oncogene
• protein kinase
• protein phosphatase
• protein phosphorylation
• tumour suppressor