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Regucalcin is a novel target of beta‐catenin in liver
Author(s) -
NejakBowen Kari N,
Zeng Gang,
Monga Satdarshan P. S.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1136-b
Subject(s) - wnt signaling pathway , biology , beta catenin , catenin , microbiology and biotechnology , carcinogenesis , medicine , endocrinology , signal transduction , gene , biochemistry
The wnt/beta‐catenin pathway plays an important role in liver biology. Because of its diverse roles in liver, it is critical to identify novel targets, which might dictate such roles. Using ?‐catenin conditional knockout mice (KO), we identified regucalcin as a novel target of this pathway. Regucalcin is a Ca2+ binding protein, which regulates Ca2+ transport from cytoplasm to nucleus in regenerating liver. mRNA e xpression of regucalcin was downregulated over 35‐fold in KO as compared to wild‐type controls (WT), which was confirmed by RT‐PCR. An analysis of regucalcin protein expression by Western blotting showed the presence of regucalcin in WT at 1, 3 & 6 months, whereas it was decreased by 1 month and absent after 3 months in KO. Immunohistochemistry confirmed normal expression of regucalcin protein in nucleus and cytosol of WT hepatocytes, which was markedly diminished in KO. Also, beta‐catenin overexpressing mice showed elevated levels of regucalcin as compared to the WT. An analysis of the promoter region of mouse regucalcin gene revealed at least 3 putative Tcf‐binding sites. Finally, regucalcin protein expression mirrors that of beta‐catenin nuclear translocation following 2/3 partial hepatectomy in the mouse. Also, higher regucalcin levels were observed in HepG2 (active‐beta‐catenin) as compared to Hep3B (normal beta‐catenin) hepatoma cells, suggesting a possible link between beta‐catenin and regucalcin in beta‐catenin‐active HCCs. In conclusion, regucalcin is regulated by beta‐catenin in the liver, and may play a role in liver regeneration and tumorigenesis.