RGD Reference Report - 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.

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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.
Authors:	Dávalos, Verónica Súarez-López, Lucía Castaño, Julio Messent, Anthea Abasolo, Ibane Fernandez, Yolanda Guerra-Moreno, Angel Espín, Eloy Armengol, Manel Musulen, Eva Ariza, Aurelio Sayós, Joan Arango, Diego Schwartz, Simó
Citation:	Dávalos V, etal., J Biol Chem. 2012 Dec 21;287(52):43472-81. doi: 10.1074/jbc.M112.428466. Epub 2012 Oct 24.
RGD ID:	151356955
Pubmed:	PMID:23095742 (View Abstract at PubMed)
PMCID:	PMC3527934 (View Article at PubMed Central)
DOI:	DOI:10.1074/jbc.M112.428466 (Journal Full-text)
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.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
SMC2	Human	colon adenocarcinoma	severity	IMP		human cell line in a mouse model	RGD
Smc2	Rat	colon adenocarcinoma	severity	ISO	SMC2 (Homo sapiens)	human cell line in a mouse model	RGD
Smc2	Mouse	colon adenocarcinoma	severity	ISO	SMC2 (Homo sapiens)	human cell line in a mouse model	RGD

Objects Annotated

Genes (Rattus norvegicus)

Smc2 (structural maintenance of chromosomes 2)

Genes (Mus musculus)

Smc2 (structural maintenance of chromosomes 2)

Genes (Homo sapiens)

SMC2 (structural maintenance of chromosomes 2)

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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.