A ubiquitin ligase complex essential for the NF-kappa B, Wnt/Wingless, and Hedgehog signaling pathways
Year: 1999
Type: preprint
Abstract: Ubiquitin-dependent proteolysis by the proteasome plays an essential role in a number of key biological processes, including cell cycle progression, transcription, and signal transduction (for review, see Peters et al. 1998).In many cases the target protein is first marked for degradation or processing by phosphorylation.The phosphorylated protein is then recognized and ubiquitinated in a process that requires three proteins (Hershko et al. 1983; for review, see Hershko 1998;Peters et al. 1998).Ubiquitin is first attached to a ubiquitin-activating enzyme (E1) in an ATP-dependent reaction to form a highenergy thiolester bond.The ubiquitin is then transferred from the E1 protein to an E2 ubiquitin-conjugating enzyme, which functions in conjunction with an E3 protein to link ubiquitin to lysine residues in the targeted protein.A specific lysine residue in the conjugated ubiquitin is then attached to a second ubiquitin, and reiteration of this process results in the assembly of a polyubiquitin chain.The polyubiquitinated protein can then be recognized by the 26S proteasome and degraded or processed. SCF ubiquitin ligase complexesE1 and E2 proteins have been identified and characterized, and the latter has been shown to comprise a family of related proteins (for review, see Peters et al. 1998).In contrast, much less is known about E3 enzymes.There are examples in which the E3 is involved directly in ubiquitin transfer (for review, see Huibregtse et al. 1998).However, in most cases E3 proteins appear to function as adapters that recruit the target protein to a complex containing an E2 enzyme, thus providing a mechanism for specificity.This mechanism is exemplified by the SCF ubiquitin ligase complex, which was initially identified in studies of the cell cycle in yeast.This complex contains the proteins Skp1, Cdc53/Cul1, and an F-box protein, as illustrated in Figure 1 (for review, see Elledge and Harper 1998;Krek 1998;Patton et al. 1998).The Cdc53/ Cul1 protein acts as scaffold for the complex, simultaneously interacting with a specific E2 protein and Skp1.
Source: Genes & Development
DOI: 10.1101/gad.13.5.505
Author: T. Maniatis
Institution: Harvard University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W1985476964