Identification of a novel ubiquitin-conjugating enzyme involved in mitotic cyclin degradation

Hongtao Yu, Randall W. King, Jan Michael Peters, Marc W. Kirschner

Research output: Contribution to journalArticle

149 Citations (Scopus)

Abstract

Background: The destruction of cyclin B is required for exit from mitosis, and is mediated by the ubiquitin pathway. Recently, a 20S complex, termed the anaphase-promoting complex (APC) or the cyclosome, has been genetically and biochemically identified as the cyclin-specific ubiquitin ligase (E3). In addition, a ubiquitin-conjugating enzyme (E2), UBC4, was shown to be involved in cyclin ubiquitination in Xenopus egg extracts. Another E2 activity, designated UBCx, can independently support cyclin ubiquitination in Xenopus. A similar activity (E2-C) has also been observed in clams. However, the molecular identity of Xenopus UBCx or clam E2-C has not been established. Results: We have purified and cloned Xenopus UBCx. Sequence comparisons with known E2s reveal that UBCx is a novel ubiquitin-conjugating enzyme. Purified recombinant UBCx is sufficient to complement purified APC and E1 in destruction box-dependent cyclin ubiquitination. UBCx and UBC4 are active in a similar concentration range and with similar kinetics. At saturating enzyme concentrations, UBCx converts twice as much substrate into ubiquitin conjugates, but generates conjugates of lower molecular mass than UBC4. Conclusions: UBCx is a novel ubiquitin-conjugating enzyme involved in cyclin ubiquitination in Xenopus. Like UBC4, ubiquitination catalyzed by UBCx is dependent on both the destruction box and the APC, suggesting that these E2s function through a similar mechanism. However, as the patterns of conjugates generated by these E2s are distinct, these enzymes may play different roles in promoting cyclin proteolysis in mitosis.

Original languageEnglish (US)
Pages (from-to)455-466
Number of pages12
JournalCurrent Biology
Volume6
Issue number4
StatePublished - 1996

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Ubiquitin-Conjugating Enzymes
ubiquitin-protein ligase
Cyclins
cyclins
Ubiquitination
Xenopus
Anaphase-Promoting Complex-Cyclosome
Degradation
degradation
Bivalvia
Ubiquitin
Mitosis
ubiquitin
clams
mitosis
Proteolysis
Cyclin B
Ubiquitin-Protein Ligases
Molecular mass
Enzymes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

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Yu, H., King, R. W., Peters, J. M., & Kirschner, M. W. (1996). Identification of a novel ubiquitin-conjugating enzyme involved in mitotic cyclin degradation. Current Biology, 6(4), 455-466.

Identification of a novel ubiquitin-conjugating enzyme involved in mitotic cyclin degradation. / Yu, Hongtao; King, Randall W.; Peters, Jan Michael; Kirschner, Marc W.

In: Current Biology, Vol. 6, No. 4, 1996, p. 455-466.

Research output: Contribution to journalArticle

Yu, H, King, RW, Peters, JM & Kirschner, MW 1996, 'Identification of a novel ubiquitin-conjugating enzyme involved in mitotic cyclin degradation', Current Biology, vol. 6, no. 4, pp. 455-466.
Yu, Hongtao ; King, Randall W. ; Peters, Jan Michael ; Kirschner, Marc W. / Identification of a novel ubiquitin-conjugating enzyme involved in mitotic cyclin degradation. In: Current Biology. 1996 ; Vol. 6, No. 4. pp. 455-466.
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