edited by Michèle Reboud-RavauxSpringer-Verlag (2002) 130 pages. ISBN 3-540-42594-2£45.50/$75
What determines the levels of a functionally active protein inside a cell?If biologists had been asked this question ten years ago the answer would probably have been very different from that given now. Then, the likely response would have been mRNA levels and/or degree of post-translational modification. Now, control of protein degradation would be a key factor to consider. Consequently, an intensive research effort is underway to identify those components and pathways that regulate this latter process.
This book presents a series of independent reviews that have a readable style and cover different aspects of protein degradation within normal and diseased cells and tissues. Our knowledge of this biological process has been increasing at an exponential rate. This book can, therefore, only hope to give a flavour of the different areas covered. Nevertheless, it provides a good starting reference for many of the topics covered through excellent up-to-date review articles.
The opening chapter enforces the concept that protein degradation in cells is not a random process. It provides examples of the complexity of selecting proteins for ubiquitin-mediated degradation. The emphasis is on the SCF-type of ubiquitin-protein ligases and, in particular, on the function of the tumor suppressor protein VHL. This was perhaps not surprising given the authors'research interests. The underlying theme of the next four chapters is the various aspects of the relationship between protein degradation and ageing in normal and diseased tissues. They describe how the removal of misfolded,mutant, oxidatively damaged or inappropriately modified proteins is dependent on the appropriate functioning of these pathways. The importance of protein degradation is also indirectly highlighted by the observation that mutations to components of these pathways include tumour suppressor proteins and proteins associated with neurodegenerative diseases. What is not generally realised, perhaps, is that targeting of proteins for degradation apparently decreases with age.
The final two chapters are concerned with describing the characteristics of the 26S proteasome and the design and use of inhibitors of proteasomal activity. Such reagents could be used to control the rates of protein degradation. This information may be particularly stimulating for those in the pharmaceutical industry seeking drug targets. Components regulating protein turnover could be considered as potential targets for novel therapeutic strategies. So, for example, the therapeutic use of specific inhibitors of the proteasome for the treatment of muscle-wasting diseases or activators of proteasomal activity for treatment of diseases associated with ageing, such as the neurodegenerative diseases. Promoting the interaction between components of E3 ligases, such as between mutated VHL and its interacting partners, may provide novel approaches for the treatment of cancer. The design of such molecules will be aided as the three-dimensional structures of components of these systems are described. At present, these include the proteasome and SCF complexes.
I would recommend this book particularly to those new to the field, such as graduate students. Those already working in this area of research, will find a number of the sections to be thought provoking and a useful reference. However, there is a danger that the rapid advances being made in this research area will quickly date its contents. The timing of this book is therefore appropriate. Those readers not familiar with the ubiquitin-26S proteasome pathway may find the repeated description of this process in many chapters useful. Others, however, may find it rather repetitive!