A Cytosolic Multiprotein Complex Containing p85α Is Required for β-Catenin Activation in Colitis and Colitis-associated Cancer.
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| Title: | A Cytosolic Multiprotein Complex Containing p85α Is Required for β-Catenin Activation in Colitis and Colitis-associated Cancer. |
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| Authors: | Goretsky, Tatiana1, Bradford, Emily M.1, Hyunji Ryu2, Tahir, Maryam1, Moyer, Mary Pat3, Tianyan Gao4, Linheng Li5, Barrett, Terrence A.1 t.barrett@uky.edu |
| Source: | Journal of Biological Chemistry. 2/19/2016, Vol. 291 Issue 8, p4166-4177. 12p. |
| Subjects: | Colitis, Intestines, Epithelial cells, Carcinogenesis, Patients |
| Abstract: | Wnt/β-catenin signaling is required for crypt structure maintenance. We previously observed nuclear accumulation of Ser- 552 phosphorylated β-catenin (pβ-CatSer-552) in intestinal epithelial cells (IEC) during colitis and colitis-associated cancer. Data here delineate a novel multiprotein cytosolic complex (MCC) involved in β-catenin signaling in the intestine. The MCC contains p85α, the class IA subunit of PI3K, along with β-catenin, 14-3-3ζ, Akt, and p110α. MCC levels in IEC increase in colitis and colitis-associated cancer patients. IEC-specific p85α-deficient (p85ΔIEC) mice develop more severe dextran sodium sulfate colitis due to delayed ulcer healing and reduced epithelial β-catenin activation. In colonic IEC, p85α deficiency did not alter PI3K signaling. In vitro shRNA depletion of individual complex members disrupts the MCC and reduces β- catenin signaling. Despite worse colitis, p85ΔIEC mice have reduced tumor burden after azoxymethane/dextran sodium sulfate treatment. Together the data indicate that the β-catenin MCC is needed for mucosal repair and carcinogenesis. This novel MCC may be an attractive therapeutic target in preventing cancer in colitis patients. [ABSTRACT FROM AUTHOR] |
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| Database: | Engineering Source |
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