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Survival of APC-mutant colorectal cancer cells requires interaction between tankyrase and a thiol peroxidase, peroxiredoxin II
- Title
- Survival of APC-mutant colorectal cancer cells requires interaction between tankyrase and a thiol peroxidase, peroxiredoxin II
- Authors
- Kang D.H.; Lee J.H.; Kang S.W.
- Ewha Authors
- 강상원
- SCOPUS Author ID
- 강상원
- Issue Date
- 2017
- Journal Title
- BMB Reports
- ISSN
- 1976-6696
- Citation
- BMB Reports vol. 50, no. 8, pp. 391 - 392
- Keywords
- Axin; Colorectal cancer; Peroxiredoxin; Tankyrase; β-catenin
- Publisher
- The Biochemical Society of the Republic of Korea
- Indexed
- SCIE; SCOPUS; KCI
- Document Type
- Article
- Abstract
- Overexpression of mammalian 2-Cys peroxiredoxin (Prx) enzymes is observed in most cancer tissues. Nevertheless, their specific roles in colorectal cancer (CRC) progression has yet to be fully elucidated. Here, a novel molecular mechanism by which PrxII/Tankyrase (TNKS) interaction mediates survival of adenomatous polyposis coli (APC)-mutant CRC cells was explored. In mice with an inactivating APC mutation, a model of spontaneous intestinal tumorigenesis, deletion of PrxII reduced intestinal adenomatous polyposis and thereby increased survival. In APC-mutant human CRC cells, PrxII depletion hindered PARP-dependent Axin1 degradation through TNKS inactivation. H2O2-sensitive Cys residues in the zincbinding domain of TNKS1 was found to be crucial for PARsylation activity. Mechanistically, direct binding of PrxII to ARC4/5 domains of TNKS conferred vital redox protection against oxidative inactivation. As a proof-of-concept experiment, a chemical compound targeting PrxII inhibited the growth of tumors xenografted with APC-mutation-positive CRC cells. Collectively, the results provide evidence revealing a novel redox mechanism for regulating TNKS activity such that physical interaction between PrxII and TNKS promoted survival of APC-mutant colorectal cancer cells by PrxII-dependent antioxidant shielding. © 2017 by the The Korean Society for Biochemistry and Molecular Biology.
- DOI
- 10.5483/BMBRep.2017.50.8.120
- Appears in Collections:
- 자연과학대학 > 생명과학전공 > Journal papers
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