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|Title:||Adenovirus E1A inhibits SCFFbw7 ubiquitin ligase||Authors:||Isobe, T.
|Issue Date:||9-Oct-2009||Citation:||Isobe, T., Hattori, T., Kitagawa, K., Uchida, C., Kotake, Y., Kosugi, I., Oda, T., Kitagawa, M. (2009-10-09). Adenovirus E1A inhibits SCFFbw7 ubiquitin ligase. Journal of Biological Chemistry 284 (41) : 27766-27779. ScholarBank@NUS Repository. https://doi.org/10.1074/jbc.M109.006809||Abstract:||The SCFFbw7 ubiquitin ligase complex plays important roles in cell growth, survival, and differentiation via the ubiquitin-proteasome-mediated regulation of protein stability. Fbw7 (also known as Fbxw7, Sel-10, hCdc4, or hAgo), a substrate recognition subunit of SCFFbw7 ubiquitin ligase, facilitates the degradation of several proto-oncogene products by the proteasome. Given that mutations in Fbw7 are found in various types of human cancers, Fbw7 is considered to be a potent tumor suppressor. In the present study, we show that E1A, an oncogene product derived from adenovirus, interferes with the activity of the SCFFbw7 ubiquitin ligase. E1A interacted with SCFFbw7 and attenuated the ubiquitylation of its target proteins in vivo. Furthermore, using in vitro purified SCFFbw7 component proteins, we found that E1A directly bound to Roc1/Rbx1 and CUL1 and that E1A inhibited the ubiquitin ligase activity of the Roc1/Rbx1-CUL1 complex but not that of another RING-type ubiquitin ligase, Mdm2. Ectopically expressed E1A interacted with cellular endogenous Roc1/Rbx1 and CUL1 and decelerated the degradation of several protooncogene products that were degraded by SCFFbw7 ubiquitin ligase. Moreover, after wild-type adenovirus infection, adenovirus-derived E1A interacted with endogenous Roc1/Rbx1 and decelerated degradation of the endogenous target protein of SCFFbw7. These observations demonstrated that E1A perturbs protein turnover regulated by SCFFbw7 through the inhibition of SCFFbw7 ubiquitin ligase. Our findings may help to explain the mechanism whereby adenovirus infection induces unregulated proliferation. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.||Source Title:||Journal of Biological Chemistry||URI:||http://scholarbank.nus.edu.sg/handle/10635/114988||ISSN:||00219258||DOI:||10.1074/jbc.M109.006809|
|Appears in Collections:||Staff Publications|
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