Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | 이창호 | - |
dc.date.accessioned | 2018-04-19T08:22:17Z | - |
dc.date.available | 2018-04-19T08:22:17Z | - |
dc.date.issued | 2012-03 | - |
dc.identifier.citation | Journal of Cell Science, 2012, 125(5), P.1284-1295 | en_US |
dc.identifier.issn | 0021-9533 | - |
dc.identifier.uri | http://jcs.biologists.org/content/125/5/1284 | - |
dc.identifier.uri | https://repository.hanyang.ac.kr/handle/20.500.11754/69532 | - |
dc.description.abstract | Nrf2 has an anti-carcinogenic effect. However, an increase in Nrf2 activity is also implicated in cancer chemoresistance. A switch from E-cadherin to N-cadherin affects the transdifferentiation and metastasis of cancer cells. In view of the key role of this switch in cancer malignancy, we investigated the regulatory effect of E-cadherin on Nrf2. In HEK293 cells, overexpression of E-cadherin inhibited the nuclear accumulation of Nrf2, and prevented Nrf2-dependent gene induction. GST pull-down and immunocytochemical assays verified the interaction between E-cadherin and Nrf2: E-cadherin bound the C-terminus of Nrf2, but not its N-terminus, which comprises the Neh2 domain responsible for phosphorylation of Ser40. Our finding that the mutation of Ser40 to alanine in Nrf2 did not affect the ability of E-cadherin to bind Nrf2 and repress target gene transactivation suggests that E-cadherin might not disturb the phosphorylation. Studies using mutant constructs of E-cadherin suggested that the beta-catenin-binding domain contributes to the inhibitory effect of E-cadherin on Nrf2. Consistently, knockdown of beta-catenin attenuated not only the effect of E-cadherin binding to Nrf2, but also Keap1-dependent ubiquitylation of Nrf2, and thereby increased Nrf2 activity, supporting the involvement of beta-catenin in the interactions. Collectively, E-cadherin recruits Nrf2 through beta-catenin, and assists the function of Keap1 for the inhibition of nuclear localization and transcriptional activity of Nrf2. In HepG2 cells, the loss of E-cadherin by either siRNA knockdown or treatment with TGF beta 1 enhanced the constitutive or inducible activity of Nrf2, implying that chemoresistance of cancer cells upon the loss of E-cadherin might be associated with Nrf2. | en_US |
dc.description.sponsorship | This work was supported by the World Class University project (Ministry of Education, Science and Technology Development) [grant number R32-2010-000-10098-0]; and a National Research Foundation of Korea grant [MEST No. 2011-0001204] funded by the Government of Korea. | en_US |
dc.language.iso | en | en_US |
dc.publisher | Company of Biologists LTD | en_US |
dc.subject | E-cadherin | en_US |
dc.subject | Nrf2 | en_US |
dc.subject | beta-catenin | en_US |
dc.subject | Keap1 | en_US |
dc.title | E-cadherin inhibits nuclear accumulation of Nrf2: implications for chemoresistance of cancer cells | en_US |
dc.type | Article | en_US |
dc.relation.no | 5 | - |
dc.relation.volume | 125 | - |
dc.identifier.doi | 10.1242/jcs.095422 | - |
dc.relation.page | 1284-1295 | - |
dc.relation.journal | JOURNAL OF CELL SCIENCE | - |
dc.contributor.googleauthor | Kim, Won Dong | - |
dc.contributor.googleauthor | Kim, Young Woo | - |
dc.contributor.googleauthor | Cho, Il Je | - |
dc.contributor.googleauthor | Lee, Chang Ho | - |
dc.contributor.googleauthor | Kim, Sang Geon | - |
dc.relation.code | 2012204794 | - |
dc.sector.campus | S | - |
dc.sector.daehak | COLLEGE OF MEDICINE[S] | - |
dc.sector.department | DEPARTMENT OF MEDICINE | - |
dc.identifier.pid | jennysue | - |
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