Varshavsky's contributions

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BAUMEISTER, Wolfgang, Andreas BACHMAIR, Vincent CHAU, Robert COHEN, Phil COFFINO, George DEMARTINO, Raymond J. DESHAIES, Juergen DOHMEN, Scott EMR, Martin SCHEFFNER, 2004. Varshavsky's contributions. In: Science. 306(5700), pp. 1290-1292. ISSN 0036-8075. eISSN 1095-9203. Available under: doi: 10.1126/science.306.5700.1290

@article{Baumeister2004Varsh-42226, title={Varshavsky's contributions}, year={2004}, doi={10.1126/science.306.5700.1290}, number={5700}, volume={306}, issn={0036-8075}, journal={Science}, pages={1290--1292}, author={Baumeister, Wolfgang and Bachmair, Andreas and Chau, Vincent and Cohen, Robert and Coffino, Phil and Demartino, George and Deshaies, Raymond J. and Dohmen, Juergen and Emr, Scott and Scheffner, Martin} }

Baumeister, Wolfgang Coffino, Phil Bachmair, Andreas Dohmen, Juergen Deshaies, Raymond J. We are writing to express our enthusiasm that the discovery of the ubiquitin conjugation system has been acknowledged with the award of the Nobel Prize in Chemistry to three outstanding biochemists: Avram Hershko and Aaron Ciechanover of the Technion Institute in Israel, and Irwin Rose of the University of California at Irvine (“Gold medal from cellular trash,” G. Vogel, News Focus, 15 Oct., p. 400). Unraveling the chemistry that underlies the attachment of ubiquitin to proteins that are destined to be degraded was a magnificent achievement and is fully deserving of this recognition.<br />The mechanism of ubiquitin conjugation and its role in proteolysis was selected for recognition by the Nobel Committee in large part because of the vital role that the ubiquitin-proteasome system (UPS) plays in the physiology of cells and organisms. Investigations on the physiological functions of the UPS, which dominate current research in this field, were pioneered largely by Alexander Varshavsky of the California Institute of Technology. Several core principles that guide our current understanding of the ubiquitin system had their origins in Varshavsky's work, including the following: (i) the UPS is the predominant mechanism for selective protein turnover in the cytoplasm and is essential for cellular function; (ii) in addition to its role in turning over damaged proteins, the UPS controls diverse physiological processes such as the cell cycle, DNA repair, and stress responses; (iii) ubiquitin ligases (E3s) are highly specific receptors that underlie the remarkable specificity of ubiquitination by binding to defined sequences within proteins (degrons); and (iv) a ubiquitin chain linked via the lysine-48 residue of ubiquitin governs targeting of substrates to the proteasome for degradation. In addition to these fundamental contributions, Varshavsky ushered the ubiquitin field into the age of molecular genetics by identifying mutants and characterizing the genes that define ubiquitin and the E1, E2, and E3 components of the conjugation cascade. In our opinion, the appreciation of the significance of the UPS owes more to Varshavsky's work than to that of any other individual.<br />We suggest that the impact of Varshavsky's work on the physiology of the ubiquitin system and its relationship to fundamental processes such as mitosis and chromosome segregation justifies serious consideration for a future Nobel Prize in Physiology or Medicine. As we extend our heartfelt congratulations to the winners of this year's Nobel Prize in Chemistry, we wish to make it clear that Varshavsky's contributions are also deeply respected by his colleagues. Demartino, George Scheffner, Martin Bachmair, Andreas 2018-05-02T08:05:15Z 2004 Scheffner, Martin Chau, Vincent Emr, Scott Cohen, Robert Chau, Vincent Cohen, Robert eng Deshaies, Raymond J. Emr, Scott 2018-05-02T08:05:15Z Varshavsky's contributions Coffino, Phil Dohmen, Juergen Demartino, George Baumeister, Wolfgang

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