NDLI: The mammalian Cut homeodomain protein functions as a cell-cycle-dependent transcriptional repressor which downmodulates p21WAF1/CIP1/SDI1 in S phase.

Content Provider	PubMed Central
Author	Coqueret, O. Bérubé, G. Nepveu, A.
Abstract	Cut is a homeodomain transcription factor which has the unusual property of containing several DNA-binding domains: three regions called Cut repeats and the Cut homeodomain. Genetic studies in Drosophila melanogaster indicate that cut plays important roles in the determination and maintenance of cell-type specificity. In the present study, we show that mammalian Cut proteins may yet play another biological role, specifically in proliferating cells. We found that the binding of Cut to a consensus binding site varies during the cell cycle. Binding was virtually undetectable in G0 and early G1, but became very strong as cells reached S phase. This was shown to result both from an increase in Cut expression and dephosphorylation of the Cut homeodomain by the Cdc25A phosphatase. We also show that the increase in Cut activity coincides with a decrease in p21WAF1/CIP1/SDI1 mRNAs. In co-transfection experiments, Cut proteins repressed p21WAF1/CIP1/SDI1 gene expression through binding to a sequence that overlaps the TATA box. Moreover, p21WAF1/CIP1/SDI1 expression was repressed equally well by either Cdc25A or Cut. Altogether, these results suggest a model by which Cdc25A activates the Cut repressor which then downregulates transcription of p21WAF1/CIP1/SDI1 in S phase. Thus, in addition to their role during cellular differentiation, Cut proteins also serve as cell-cycle-dependent transcriptional factors in proliferating cells.
Related Links	http://dx.doi.org/10.1093/emboj/17.16.4680
Ending Page	4694
Page Count	15
Starting Page	4680
File Format	PDF
ISSN	14602075
e-ISSN	14602075
Journal	The EMBO Journal
Issue Number	16
Volume Number	17
Language	English
Publisher Date	1998-05-01
Access Restriction	Open
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Immunology and Microbiology(all) Neuroscience(all) Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Neuroscience Immunology and Microbiology Medicine Molecular Biology

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