Human SMC2 protein, a core subunit of human condensin complex, is a novel transcriptional target of the WNT signaling pathway and a new therapeutic target

Verónica Dávalos, Lucía Súarez-López, Julio Castaño, Anthea Messent, Ibane Abasolo, Yolanda Fernandez, Angel Guerra-Moreno, Eloy Espín, Manel Armengol, Eva Musulen, Aurelio Ariza, Joan Sayós, Diego Arango, Simó Schwartz

Research output: Contribution to journalArticleResearchpeer-review

25 Citations (Scopus)

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 SMC 2 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. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc.
Original languageEnglish
Pages (from-to)43472-43481
JournalJournal of Biological Chemistry
Volume287
DOIs
Publication statusPublished - 21 Dec 2012

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