Early mitotic degradation of the homeoprotein HOXC10 is potentially linked to cell cycle progression.
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.
Gabellini
Davide
D
Istituto di Genetica Molecolare, CNR, via Abbiategrasso 207,I-27100 Pavia, Italy.
Colaluca
Ivan N
IN
Vodermaier
Hartmut C
HC
Biamonti
Giuseppe
G
Giacca
Mauro
M
Falaschi
Arturo
A
Riva
Silvano
S
Peverali
Fiorenzo A
FA
D064191:Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008938:Mitosis / Q000502:physiology*; D009097:Multienzyme Complexes / Q000378:metabolism; D009154:Mutation; D046988:Proteasome Endopeptidase Complex; D011994:Recombinant Proteins / Q000378:metabolism; D015533:Transcriptional Activation; D014452:Ubiquitins / Q000378:metabolism
D064191:Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome; C577366:CDC27 protein, human; D018797:Cell Cycle Proteins; D002843:Chromatin; C410304:HOXC10 protein, human; D018398:Homeodomain Proteins; D009097:Multienzyme Complexes; D011994:Recombinant Proteins; D014452:Ubiquitins; D005982:Glutathione Transferase; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex