| Cell cycle regulation of the human Six1 homeoprotein is mediated by APC(Cdh1). | |
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MedLine Citation:
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PMID: 17130831 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The Six1 homeoprotein is an important mediator of normal development, where it is critical for the proliferation of precursor cell populations that ultimately constitute the muscle, kidney and inner ear, among other organs. Interestingly, its overexpression has been observed in numerous cancers, where it contributes to the proliferative and metastatic ability of the cancer cells. Here we show that Six1 not only regulates the cell cycle, but is itself regulated throughout the cell cycle via ubiquitin-mediated proteolysis. The protein is present from the G(1)/S boundary until mitosis, when it is degraded via the anaphase-promoting complex (APC) with its activating subunit Cdh1. However, unlike most identified APC(Cdh1) targets, Six1 does not contain functional destruction or KEN box motifs that are necessary for its degradation. Instead, the Six1 protein contains multiple, as yet undefined, sequences within its N- and C-termini responsible for its degradation, including an N-terminal region that binds to Cdh1. Cell cycle regulation of Six1 occurs both transcriptionally and post-translationally via phosphorylation; therefore, this study demonstrates a third and novel mechanism of cell cycle-specific regulation of Six1, underscoring the importance of confining its activity to a defined cell cycle window from the G(1)/S boundary to early mitosis. |
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Authors:
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K L Christensen; J D G Brennan; C S Aldridge; H L Ford |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. Date: 2006-11-20 |
Journal Detail:
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Title: Oncogene Volume: 26 ISSN: 0950-9232 ISO Abbreviation: Oncogene Publication Date: 2007 May |
Date Detail:
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Created Date: 2007-05-17 Completed Date: 2007-06-18 Revised Date: 2007-12-03 |
Medline Journal Info:
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Nlm Unique ID: 8711562 Medline TA: Oncogene Country: England |
Other Details:
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Languages: eng Pagination: 3406-14 Citation Subset: IM |
Affiliation:
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Program in Molecular Biology, University of Colorado at Denver and Health Sciences Center, Fitzsimons Campus, Aurora, CO, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Motifs Amino Acid Sequence Cadherins / genetics, metabolism* Cell Cycle* Cell Line, Tumor Cell Nucleus / metabolism Homeodomain Proteins / chemistry, genetics, metabolism* Humans Proteasome Endopeptidase Complex / metabolism Protein Binding Ubiquitin / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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R01 CA095277/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/CDH1 protein, human; 0/Cadherins; 0/Homeodomain Proteins; 0/SIX1 protein, human; 0/Ubiquitin; EC 3.4.25.1/Proteasome Endopeptidase Complex |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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