The ubiquitin signal: assembly, recognition and termination

Abstract

The Ubiquitin and Signaling Meeting was a Keystone Symposium organized by T. Hunter, C. Joazeiro and M. Hochstrasser and was held in Taos, New Mexico, between 22 and 27 February 2005. ![][1] The 2004 Nobel Prize in Chemistry was awarded to I. Rose, A. Ciechanover and A. Hershko for their groundbreaking discovery of ubiquitin‐dependent proteolysis in the late 1970s (Wilkinson, 2004). In the subsequent 25 years, we have become aware that the ubiquitin (Ub) domain acts as a targeting signal for numerous events in the cell. The addition of a single Ub to target proteins is involved in histone structure and transcriptional control, as well as receptor internalization and endosomal sorting. The addition of multiple Ub molecules, usually as a polyubiquitin chain, is involved in degradation by the proteasome, DNA repair, ribosomal function, signal transduction, and other less well understood processes. Besides Ub‐mediated protein modification, the cell uses similar enzymatic machinery to conjugate several Ub‐like proteins (Ubl) to target proteins (Schwartz & Hochstrasser, 2003). Like monoubiquitylation, most conjugation of Ubl to substrates seems to be associated with non‐proteolytic functions. Examples include: Nedd8 (neuronally expressed during development 8), a Ubl that is conjugated to the cullin component of Ub ligases and regulates assembly of the active ligase complex; SUMO (small Ub‐related modifier), a distant relative of Ub involved in modulating protein activity and nuclear localization; and ISG15 (interferon stimulated gene product 15), a 15 kDa protein containing two Ub domains that is conjugated to cellular proteins in response to interferon, lipopolysaccharide (LPS) and other inflammatory signals. Figure 1 summarizes the functions that have been ascribed to Ub‐mediated protein modification. Figure 1. Assembly and fates of various forms of the ubiquitin domain. The E1 activating enzyme adenylates the carboxyl terminus of ubiquitin (Ub) and then forms a thiolester with the E2 conjugating enzymes that act … [1]: pending:yes