Abstract
Human SMC2 is part of the condensin complex, which is responsible for tightly packaging replicated genomic DNA prior to segregation into daughter cells. Engagement of the WNT signaling pathway is known to have a mitogenic effect on cells, but relatively little is known about WNT interaction with mitotic structural organizer proteins. In this work, we described the novel transcriptional regulation of SMC2 protein by direct binding of the β-catenin·TCF4 transcription factor to the SMC2 promoter. Furthermore, we identified the precise region in the SMC2 promoter that is required for β-catenin-mediated promoter activation. Finally, we explored the functional significance of down-regulating SMC2 protein in vivo. Treatment of WNT-activated intestinal tumor cells with SMC2 siRNA significantly reduced cell proliferation in nude mice, compared with untreated controls (p = 0.02). Therefore, we propose that WNT signaling can directly activate SMC2 transcription as a key player in the mitotic cell division machinery. Furthermore, SMC2 represents a new target for oncological therapeutic intervention.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine Triphosphatases / genetics
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Adenosine Triphosphatases / metabolism*
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Animals
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism*
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cell Cycle Proteins
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Cell Line, Tumor
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Humans
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Macaca
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Mice
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Mice, Nude
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Mitosis / genetics
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Multiprotein Complexes / genetics
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Multiprotein Complexes / metabolism*
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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Neoplasm Transplantation
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Neoplasms / genetics
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Neoplasms / metabolism*
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Neoplasms / therapy
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism*
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Pan troglodytes
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Promoter Regions, Genetic
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Protein Binding
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Rats
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Transcription Factor 4
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcription, Genetic / genetics
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Transplantation, Heterologous
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Wnt Signaling Pathway*
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beta Catenin / genetics
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beta Catenin / metabolism
Substances
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Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
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Carrier Proteins
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Cell Cycle Proteins
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DNA-Binding Proteins
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Multiprotein Complexes
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Neoplasm Proteins
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Nuclear Proteins
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SMC2 protein, human
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TCF4 protein, human
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Transcription Factor 4
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Transcription Factors
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beta Catenin
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condensin complexes
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Adenosine Triphosphatases