Article

Chen ZJ, Sun LJ.. Nonproteolytic functions of ubiquitin in cell signaling. Mol Cell 33: 275-286

Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
Molecular cell (Impact Factor: 14.02). 03/2009; 33(3):275-86. DOI: 10.1016/j.molcel.2009.01.014
Source: PubMed

ABSTRACT

The small protein ubiquitin is a central regulator of a cell's life and death. Ubiquitin is best known for targeting protein destruction by the 26S proteasome. In the past few years, however, nonproteolytic functions of ubiquitin have been uncovered at a rapid pace. These functions include membrane trafficking, protein kinase activation, DNA repair, and chromatin dynamics. A common mechanism underlying these functions is that ubiquitin, or polyubiquitin chains, serves as a signal to recruit proteins harboring ubiquitin-binding domains, thereby bringing together ubiquitinated proteins and ubiquitin receptors to execute specific biological functions. Recent advances in understanding ubiquitination in protein kinase activation and DNA repair are discussed to illustrate the nonproteolytic functions of ubiquitin in cell signaling.

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    • "These complex and varied structures enable ubiquitination to transmit diverse functional signals that determine the fate of a substrate protein. The well-studied K63-linked chains mediate the functions of various cellular proteins involved in inflammatory signaling complexes, whereas K48-linked chains predominantly facilitate the proteasomal-mediated degradation of substrates (Hershko and Ciechanover, 1998; Chen and Sun, 2009). To date, other types of ubiquitin linkages have not been well studied and are usually referred to as atypical ubiquitinations. "
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    • "These complex and varied structures enable ubiquitination to transmit diverse functional signals that determine the fate of a substrate protein. The well-studied K63-linked chains mediate the functions of various cellular proteins involved in inflammatory signaling complexes, whereas K48-linked chains predominantly facilitate the proteasomal-mediated degradation of substrates (Hershko and Ciechanover, 1998; Chen and Sun, 2009). To date, other types of ubiquitin linkages have not been well studied and are usually referred to as atypical ubiquitinations. "
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    Full-text · Dataset · Dec 2015
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    • "Different linkages have different functional specificities [7]. Lys48- and Lys63-linked polyUb chains are linked to protein degradation [8] and cellular signaling [9], whereas the role of the remaining Ub chain types, often indicated as " atypical " chains, is less understood [10]. Lys11 and Met1 linkages seem to be involved in cell cycle regulation and nuclear factor-kB activation, respectively [11] [12]. "
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