Mellon Lecture

Recent Discoveries about the Ubiquitin System and the N-End Rule Pathway
11:00 a.m., Friday, 4 October

Alexander Varshavsky, PhD
Howard and Gwen Laurie Smits Professor of Cell Biology, California Institute of Technology


The results of fundamental biological studies by Alexander Varshavsky, PhD, are critical to our understanding of cancer, neurodegeneration, infections, birth defects, and many other illnesses. He received his PhD in biochemistry from the Institute of Molecular Biology in Moscow, Russia, in 1973. In 1977, he emigrated to the United States and joined the Department of Biology at the Massachusetts Institute of Technology.

In the 1980s, Varshavsky discovered the first biological functions of the ubiquitin system and demonstrated the central role of regulated protein degradation in cellular physiology. He also discovered the first degradation signals in short-lived proteins (including the N-end rule) and the first ubiquitin-conjugating enzymes with defined physiological functions. Varshavsky identified and then cloned the first specific ubiquitin ligase, UBR1, which mediates the N-end rule pathway. These and related studies by the Varshavsky laboratory created the field of ubiquitin biology, which has become one of the largest areas of biomedical science.

Outside the ubiquitin field, Varshavsky discovered the first nucleosome-depleted, nuclease-hypersensitive sites at the transcriptional promoters and replication origins, and the first pathway of chromosome cohesion/segregation, mediated by multicatenated DNA. He is also an inventor of major methods in biochemistry and genetics, including the ubiquitin fusion technique, the chromatin immunoprecipitation (ChIP) assay, and the split-ubiquitin assay for in vivo protein interactions.

Varshavsky’s many awards include the Gairdner International Award, the Albert Lasker Basic Medical Research Award, the Sloan Prize, the Wolf Prize in Medicine, the Louisa Gross Horwitz Prize, the Stein and Moore Award, the Otto Warburg Medal, the King Faisal International Prize for Science, the Schleiden Medal, and the Vilcek Prize in Biomedical Science. He is a member of the National Academy of Sciences and the American Academy of Arts and Sciences.

Varshavsky delivered the Klaus Hofmann Lecture at Science 2004: No Boundaries.