1Brief History of Protein Degradation and the Ubiquitin System

The reader of this book may be impressed (and possibly overwhelmed) by the enor-mous recent progress in this field. The ubiquitin system is now known to be in-volved in basic biological processes, such as the control of cell division, signal transduction, regulation of transcription, DNA repair, quality control in the endo-plasmic reticulum, stress response, induction of immune response and inflamma-tion, apoptosis, embryonic development, and circadian clocks, to mention but a few. It has been implicated in diseases such as many types of cancer, neurodege-nerative diseases (such as certain types of Parkinson’s, Alzheimer’s and Hunting-ton’s diseases), retroviral infections, certain types of hypertension, mental retarda-tion, and cachexia associated with cancer, renal failure, or sepsis. New functions of ubiquitin and of ubiquitin-like proteins are being reported almost every month, and the number of publications in this field is increasing at an exponential (and bewildering!) rate. It may be therefore instructive to consider briefly the humble beginnings of this field, how significant progress was achieved, and also how at times progress was impeded by wrong dogmas. Important lessons can be learned from both achievements and failures in science