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Paul, D. and Islam, S. and Manne, R.K. and Dinesh, U.S. and Malonia, S.K. and Maity, B. and Boppana, R. and Rapole, S. and Shetty, P. and Santra, M.K. (2019) F-box protein FBXO16 functions as a tumor suppressor by attenuating nuclear - catenin function. Journal of Pathology, 164 (5). pp. 1433-1439.

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Aberrant activation of β‐catenin has been implicated in a variety of human diseases including cancer. In spite of significant progress, the regulation of active Wnt/β‐catenin signaling pathway is still poorly understood. In this study, we show that F‐box protein 16 (FBXO16) is a putative tumor suppressor. It is a component of SCF (SKP1‐Cullin1‐F‐box protein) complex, which targets nuclear β‐catenin protein for facilitating proteasomal degradation through the 26S proteasome. FBXO16 interacts physically with the C‐terminal domain of β‐catenin and promotes its lysine 48 linked polyubiquitination. Additionally, it inhibits epithelial to mesenchymal transition (EMT) by attenuating the level of β‐catenin. Therefore, depletion of FBXO16 leads to increased levels of β‐catenin, which then promotes cell invasion, tumor growth and EMT of cancer cells. Further, FBXO16 and β‐catenin share an inverse correlation of cellular expression in clinical breast cancer patient samples. In summary, we propose that FBXO16 functions as a putative tumor suppressor by forming an SCFFBXO16 complex that targets nuclear β‐catenin in a unique manner for ubiquitination and subsequent proteasomal degradation to prevent malignancy. This work suggests a novel therapeutic strategy against human cancers related to aberrant β‐catenin activation.

Item Type: Article
Depositing User: Mr. Rameshwar Nema
Date Deposited: 21 Feb 2020 05:23
Last Modified: 21 Feb 2020 05:23
URI: http://nccs.sciencecentral.in/id/eprint/732

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