Publications
Detailed Information
Overactivated NRF2 induces pseudohypoxia in hepatocellular carcinoma by stabilizing HIF-1 alpha
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Zheng, Jie | - |
dc.contributor.author | Kim, Su-Jung | - |
dc.contributor.author | Saeidi, Soma | - |
dc.contributor.author | Kim, Seong Hoon | - |
dc.contributor.author | Fang, Xizhu | - |
dc.contributor.author | Lee, Yeon-Hwa | - |
dc.contributor.author | Guillen-Quispe, Yanymee N. | - |
dc.contributor.author | Ngo, Hoang Kieu Chi | - |
dc.contributor.author | Kim, Do-Hee | - |
dc.contributor.author | Kim, Doojin | - |
dc.contributor.author | Surh, Young-Joon | - |
dc.date.accessioned | 2023-05-10T01:23:07Z | - |
dc.date.available | 2023-05-10T01:23:07Z | - |
dc.date.created | 2023-03-23 | - |
dc.date.created | 2023-03-23 | - |
dc.date.created | 2023-03-23 | - |
dc.date.created | 2023-03-23 | - |
dc.date.issued | 2023-01 | - |
dc.identifier.citation | Free Radical Biology and Medicine, Vol.194, pp.347-356 | - |
dc.identifier.issn | 0891-5849 | - |
dc.identifier.uri | https://hdl.handle.net/10371/192272 | - |
dc.description.abstract | Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is highly expressed/activated in most hypoxic tumors including hepato-cellular carcinoma (HCC). Another key transcription factor, nuclear factor erythroid 2-related factor 2 (NRF2), is also constitutively overactivated in HCC. In an attempt to determine whether HIF-1 alpha and NRF2 could play complementary roles in HCC growth and progression, we investigated the crosstalk between these two tran-scription factors and underlying molecular mechanisms in cultured HCC cells and experimentally induced hepatocarcinogenesis as well as clinical settings. While silencing of HIF-1 alpha in HepG2 human hepatoma cells did not alter the protein expression of NRF2, NRF2 knockdown markedly reduced the nuclear accumulation of HIF-1 alpha without influencing its mRNA expression. In diethylnitrosamine-induced hepatocarcinogenesis in wild type mice, there was elevated NRF2 expression with concomitant upregulation of HIF-1 alpha. However, this was abol-ished in Nrf2 knockout mice. NRF2 and HIF-1 alpha co-localized and physically interacted with each other as assessed by in situ proximity ligation and immunoprecipitation assays. In addition, the interaction between NRF2 and HIF-1 alpha as well as their overexpression was found in tumor specimens obtained from HCC patients. In normoxia, HIF-1 alpha undergoes hydroxylation by a specific HIF-prolyl hydroxylase domain protein (PHD), which facilitates ubiquitination and proteasomal degradation of HIF-1 alpha. NRF2 contributes to pseudohypoxia, by directly binding to the oxygen-dependent degradation (ODD) domain of HIF-1 alpha, which hampers the PHD2-mediated hydroxyl-ation, concomitant recruitment of von-Hippel-Lindau and ubiquitination of HIF-1 alpha. | - |
dc.language | 영어 | - |
dc.publisher | Elsevier BV | - |
dc.title | Overactivated NRF2 induces pseudohypoxia in hepatocellular carcinoma by stabilizing HIF-1 alpha | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/j.freeradbiomed.2022.11.039 | - |
dc.citation.journaltitle | Free Radical Biology and Medicine | - |
dc.identifier.wosid | 000910158800001 | - |
dc.identifier.scopusid | 2-s2.0-85144733190 | - |
dc.citation.endpage | 356 | - |
dc.citation.startpage | 347 | - |
dc.citation.volume | 194 | - |
dc.description.isOpenAccess | N | - |
dc.contributor.affiliatedAuthor | Surh, Young-Joon | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.subject.keywordPlus | HYPOXIA-INDUCIBLE FACTOR-1-ALPHA | - |
dc.subject.keywordPlus | PROLYL HYDROXYLASES PHD1 | - |
dc.subject.keywordPlus | FACTOR-I | - |
dc.subject.keywordPlus | HIF-1 | - |
dc.subject.keywordPlus | ACTIVATION | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordPlus | RESPONSES | - |
dc.subject.keywordPlus | COMPLEX | - |
dc.subject.keywordAuthor | Hepatocellular carcinoma | - |
dc.subject.keywordAuthor | Hypoxia | - |
dc.subject.keywordAuthor | NRF2 | - |
dc.subject.keywordAuthor | HIF-1? | - |
dc.subject.keywordAuthor | Pseudohypoxia | - |
- Appears in Collections:
- Files in This Item:
- There are no files associated with this item.
Item View & Download Count
Items in S-Space are protected by copyright, with all rights reserved, unless otherwise indicated.