Stephen J. Elledge, Ph.D.

Biochemistry & Molecular Biology
Howard Hughes Medical Institute

Jeffrey Wade Harper, Ph.D.

Biochemistry & Molecular Biology

Mechanism of regulated protein stability; discovery of SCF ubiquitin ligase pathway

Drs. Elledge and Harper received the award for their seminal studies on the fundamental mechanism of regulated protein proteolysis. Through analysis of the pathways that control the destruction of cyclins and cyclin-dependent kinase inhibitors, they have discovered a modular ubiquitin ligase system, the SCF ubiquitin ligase, which is responsible for the regulated destruction of hundreds and possibly thousands of proteins. Mutations in components of these systems are implicated in cancer and developmental abnormalities. Moreover, there are multiple examples in which viruses such as HIV have co-opted these ubiquitin ligase pathways in order to subvert normal control mechanisms in the cell.

Dr. Elledge and Harper’s nomination was based on the following publications:

Skowyra D, Craig KL, Tyers M, Elledge SJ, Harper JW." F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex. ". Cell. 1997 Oct 17;91(2):209-19

Skowyra D, Koepp DM, Kamura T, Conrad MN, Conaway RC, Conaway JW, Elledge SJ, Harper JW. " Reconstitution of G1 cyclin ubiquitination with complexes containing SCFGrr1 and Rbx1. ". Science. 1999 Apr 23;284(5414):662-5.

Winston JT, Strack P, Beer-Romero P, Chu CY, Elledge SJ, Harper JW. " The SCFbeta-TRCP-ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IkappaBalpha and beta-catenin and stimulates IkappaBalpha ubiquitination in vitro.". Genes Dev. 1999 Feb 1;13(3):270-83.