Cell Biology

Reading the Signs

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Science  13 Mar 2009:
Vol. 323, Issue 5920, pp. 1407
DOI: 10.1126/science.323.5920.1407b

Posttranslational modifications are one of many ways to control the activity of proteins. Ubiquitin is a small molecule that is covalently attached to target proteins and regulates the function of many different biological processes. In yeast, up to 20% of proteins can be conjugated to ubiquitin, and all seven conserved lysine (K) residues in ubiquitin itself can be used to form both branched and linear polypeptide chains. These different combinations are thought to mark proteins for different cellular fates. The most abundant chain is linked through K48, which targets the associated proteins for degradation by the proteasome. K63-linked ubiquitin chains were previously thought to regulate proteasome-independent functions in vivo, such as DNA repair. Now, Saeki et al. have found that K63-linked ubiquitin can also target proteins to the proteasome. Using Saccharomyces cerevisiae, they studied the topology of the ubiquitin chains formed by the E3 ubiquitin ligase Rsp5, which is known to regulate both proteasome-dependent and -independent functions. In vitro, Rsp5 was found to generate only K63-linked ubiquitin chains, which were then unexpectedly recognized by the proteasome. Further in vivo studies showed K63-linked ubiquitin chains bound to the proteasome, suggesting that, like K48-linkages, K63-links may also have an extensive role in regulating protein degradation. — HP*

EMBO J. 28, 359 (2009).

  • * Helen Pickersgill is a locum editor in Science's editorial department.

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