Ubiquitin is a small polypeptide that is conjugated to proteins and commonly serves as a degradation signal. The attachment of ubiquitin (Ub) to a substrate proceeds through a multi-enzyme cascade involving an activating enzyme (E1), a conjugating enzyme (E2), and a protein ligase (E3). We previously demonstrated that a murine E2, UbcM2, is imported into nuclei by the transport receptor importin-11. We now show that the import mechanism for UbcM2 and two other human class III E2s (UbcH6 and UBE2E2) uniquely requires the covalent attachment of Ub to the active site cysteine of these enzymes. This coupling of E2 activation and transport arises from the selective interaction of importin-11 with the Ub-loaded forms of these enzymes. Together, these findings reveal that Ub charging can function as a nuclear import trigger, and identify a novel link between E2 regulation and karyopherin-mediated transport.
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22 November 2004
Article|
November 15 2004
Ubiquitin charging of human class III ubiquitin-conjugating enzymes triggers their nuclear import
Scott M. Plafker,
Scott M. Plafker
1Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104
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Kendra S. Plafker,
Kendra S. Plafker
1Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104
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Allan M. Weissman,
Allan M. Weissman
2Laboratory of Protein Dynamics and Signaling, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702
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Ian G. Macara
Ian G. Macara
3Center for Cell Signaling and Department of Microbiology, University of Virginia, Charlottesville, VA 22908
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Scott M. Plafker
1Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104
Kendra S. Plafker
1Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104
Allan M. Weissman
2Laboratory of Protein Dynamics and Signaling, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702
Ian G. Macara
3Center for Cell Signaling and Department of Microbiology, University of Virginia, Charlottesville, VA 22908
Correspondence to Scott M. Plafker: [email protected]
Abbreviations used in this paper: β-ME, β-mercaptoethanol; CBB, Coomassie brilliant blue; E1, ubiquitin-activating enzyme; E2, ubiquitin-conjugating enzyme; E3, ubiquitin protein ligase; HEK, human embryonic kidney; RRL, rabbit reticulocyte lysate; Ub, ubiquitin; UBC, catalytic core domain; wt, wild type.
Received:
June 01 2004
Accepted:
September 24 2004
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2004
J Cell Biol (2004) 167 (4): 649–659.
Article history
Received:
June 01 2004
Accepted:
September 24 2004
Citation
Scott M. Plafker, Kendra S. Plafker, Allan M. Weissman, Ian G. Macara; Ubiquitin charging of human class III ubiquitin-conjugating enzymes triggers their nuclear import . J Cell Biol 22 November 2004; 167 (4): 649–659. doi: https://doi.org/10.1083/jcb.200406001
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