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Volume 21, Issue 5; h5 s8 ]7 N: H' J( O# q( G# O
On the cover: Posttranslational modification with polymeric chains of ubiquitin allows proteins to enter many divergent signaling pathways depending on how ubiquitins are linked to each other in the chain. Research on ubiquitin signaling has focused primarily on homogeneously linked polyubiquitin chains. Although polyubiquitins containing different linkages within the same chain occur in vivo, the structural and functional outcomes of linkage mixing and branching are poorly understood. Nakasone et al. (pp. 727–740) show that Lys48 and Lys63 linkages retain their distinctive structural and signaling properties in mixed-linkage branched and unbranched triubiquitin chains. The ability to encode multiple signals in the same chain can vastly expand the signaling repertoire of polyubiquitin. The cover depicts structural models of the branched and unbranched triubiquitins containing both Lys48 and Lys63 linkages and uses an iceberg allegory to emphasize the vastness of possible mixed-linkage polyubiquitin signals. Cover concept by Mark A. Nakasone. ©iStockphoto.com/ResearchJournals
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