Early mitotic degradation of the homeoprotein HOXC10 is potentially linked to cell cycle progression

Davide Gabellini, Ivan N. Colaluca, Hartmut C. Vodermaier, Giuseppe Biamonti, Mauro Giacca, Arturo Falaschi, Silvano Riva, Fiorenzo A. Peverali

Research output: Contribution to journalArticle

Abstract

Hox proteins are transcription factors involved in controlling axial patterning, leukaemias and hereditary malformations. Here, we show that HOXC10 oscillates in abundance during the cell cycle, being targeted for degradation early in mitosis by the ubiquitin-dependent proteasome pathway. Among abdominal-B subfamily members, the mitotic proteolysis of HOXC10 appears unique, since the levels of the paralogous HOXD10 and the related homeoprotein HOXC13 are constant throughout the cell cycle. When two destruction box motifs (D-box) are mutated, HOXC10 is stabilized and cells accumulate in metaphase. HOXC10 appears to be a new prometaphase target of the anaphase-promoting complex (APC), since its degradation coincides with cyclin A destruction and is suppressed by expression of a dominant-negative form of UbcH10, an APC-associated ubiquitin-conjugating enzyme. Moreover, HOXC10 co-immunoprecipitates the APC subunit CDC27, and its in vitro degradation is reduced in APC-depleted extracts or by competition with the APC substrate cyclin A. These data imply that HOXC10 is a homeoprotein with the potential to influence mitotic progression, and might provide a link between developmental regulation and cell cycle control.

Original languageEnglish
Pages (from-to)3715-3724
Number of pages10
JournalEMBO Journal
Volume22
Issue number14
DOIs
Publication statusPublished - Jul 15 2003

Keywords

  • Cell cycle
  • Hox
  • Mitosis
  • Origin of DNA replication
  • Ubiquitin

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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    Gabellini, D., Colaluca, I. N., Vodermaier, H. C., Biamonti, G., Giacca, M., Falaschi, A., Riva, S., & Peverali, F. A. (2003). Early mitotic degradation of the homeoprotein HOXC10 is potentially linked to cell cycle progression. EMBO Journal, 22(14), 3715-3724. https://doi.org/10.1093/emboj/cdg340