Kaiser___Huang_2005 - Review Global approaches to...

Info iconThis preview shows pages 1–2. Sign up to view the full content.

View Full Document Right Arrow Icon
Genome Biology 2005, 6: 233 comment reviews reports deposited research interactions information refereed research Review Global approaches to understanding ubiquitination Peter Kaiser* and Lan Huang †‡ Addresses: *Department of Biological Chemistry, School of Medicine, Department of Physiology and Biophysics, and Department of Developmental and Cell Biology, University of California, Irvine, CA 92697-1700, USA. Correspondence: Peter Kaiser. E-mail: [email protected] Abstract Ubiquitination - the linkage of one or more molecules of the protein ubiquitin to another protein - regulates a wide range of biological processes in all eukaryotes. We review the proteome-wide strategies that are being used to study aspects of ubiquitin biology, including substrates, components of the proteasome and ubiquitin ligases, and deubiquitination. Published: 29 September 2005 Genome Biology 2005, 6: 233 (doi:10.1186/gb-2005-6-10-233) The electronic version of this article is the complete one and can be found online at http://genomebiology.com/2005/6/10/233 © 2005 BioMed Central Ltd Ubiquitin, a small protein of 76 amino acids, is highly con- served in all eukaryotes. In a multi-step process, ubiquitin is covalently linked to lysine residues of substrate proteins. If a single molecule of ubiquitin is linked to a protein, this is referred to as mono-ubiquitination, a process that is of partic- ular importance for protein trafficking but has also been shown to regulate retrovirus budding and to modulate protein function directly [1]. A lysine residue of a ubiquitin molecule attached to a substrate can itself serve as an accep- tor for an additional ubiquitin molecule, and this process can be repeated so that poly-ubiquitinated proteins form. Poly- ubiquitin chains serve as recognition signals for the 26S pro- teasome, the major regulator of protein abundance in cells, and poly-ubiquitination thus often initiates proteolysis of the substrate. But poly-ubiquitination can also regulate protein function directly without affecting stability, in ways similar to mono-ubiquitination and other post-translational modifica- tions. The mechanisms underlying proteolysis-independent regulation by poly-ubiquitination are only poorly understood but might function by changing conformation or adding or obscuring a binding site (Figure 1; for reviews see [1-3]). The transfer of ubiquitin is a multi-step process that involves at least three classes of enzymes: ubiquitin-activating enzymes, generally called E1 enzymes; ubiquitin-conjugating enzymes or E2s; and ubiquitin ligases, E3s (Figure 1). E3 ubiquitin ligases are of particular importance because they confer substrate specificity to the system by interacting directly with substrate proteins and thereby directing the transfer of ubiquitin. The human genome encodes an esti- mated 500-600 ubiquitin ligases, a number comparable to the 518 predicted kinases [4,5]. If you consider that each ubiquitin ligase is active on several substrates, you can get
Background image of page 1

Info iconThis preview has intentionally blurred sections. Sign up to view the full version.

View Full DocumentRight Arrow Icon
Image of page 2
This is the end of the preview. Sign up to access the rest of the document.

This note was uploaded on 05/28/2010 for the course WE BIBI000000 taught by Professor Johangrooten during the Spring '10 term at Ghent University.

Page1 / 8

Kaiser___Huang_2005 - Review Global approaches to...

This preview shows document pages 1 - 2. Sign up to view the full document.

View Full Document Right Arrow Icon
Ask a homework question - tutors are online