The rockefeller university

Event Details

Type

Friday Lecture Series

Speaker(s)

Alexander Varshavsky, Ph.D., Howard and Gwen Laurie Smits Professor of Cell Biology, California Institute of Technology

Speaker bio(s)

The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. The multifunctional N-end rule pathway recognizes proteins containing N-terminal degradation signals called N-degrons, polyubiquitylates these proteins and thereby causes their degradation by the proteasome. The main determinant of an N-degron is a destabilizing N-terminal residue of a protein. The N-end rule pathway consists of two branches. One of them, called the Ac/N-end rule pathway, recognizes and destroys intracellular proteins bearing N-terminally acetylated residues. The other branch, called the Arg/N-end rule pathway, targets proteins bearing specific unacetylated N-terminal residues. The wide-ranging functions of the N-end rule pathway include the selective destruction of misfolded or otherwise abnormal proteins; the sensing of heme, nitric oxide and oxygen; the regulation of G proteins, peptide import, DNA repair, meiosis, spermatogenesis, neurogenesis, cardiovascular development and the cohesion/segregation of chromosomes. Recognition components of the N-end rule pathway are called N-recognins. In eukaryotes, N-recognins are E3 ubiquitin ligases that can target N-degrons. Prokaryotes (bacteria and archaea) lack the bona fide ubiquitin system. Nevertheless, all examined bacteria, and apparently archaea as well, contain the N-end rule pathway, ubiquitin-independent versions of it. Dr. Varshavsky will discuss recent advances in understanding the N-end rule pathway, including its role in the control of subunit stoichiometries in oligomeric proteins and its functions as a mechanistically specific repressor of apoptosis and neurodegeneration.

 

Dr. Varshavsky earned his Ph.D. in biochemistry from the Institute of Molecular Biology in Moscow in 1973, and was a research fellow there until 1976. He joined the faculty of the Massachusetts Institute of Technology in 1977 and became professor of biology there in 1986. Dr. Varshavsky joined the California Institute of Technology in 1992 as the Howard and Gwen Laurie Smits Professor of Cell Biology. Among his many honors, Dr. Varshavsky received the Gairdner International Award in 1999, the Lasker Award in Basic Medical Research in 2000, the Massry Prize in 2001 and the King Faisal International Prize in Science in 2012. Dr. Varshavsky is a fellow of the American Academy of Arts and Sciences, a member of the National Academy of Sciences, a fellow of the American Association for Advancement of Science and a foreign member of the European Academy of Sciences.

Open to

Public

Host

Jeffrey Friedman

Reception

Refreshments, 3:15 p.m. - 3:45 p.m., Abby Lounge

Contact

Gloria Phipps

Phone

(212) 327-8967

Sponsor

Gloria Phipps
(212) 327-8967
phippsg@rockefeller.edu