FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2160086543> ?p ?o ?g. }

• W2160086543 endingPage "11869" @default.
• W2160086543 startingPage "11859" @default.
• W2160086543 abstract "Disruption of the microtubule cytoskeleton impairs tumor angiogenesis by inhibiting the hypoxia-inducible factor (HIF-1α) pathway. However, the signaling cascade linking microtubule disruption to HIF-1α inactivation has not been elucidated. Here, we show that microtubule-targeting drug (MTD) treatment impaired HIF-1α protein nuclear translocation, which significantly down-regulated HIF transcriptional activity. We provide strong evidence that HIF-1α protein associates with polymerized microtubules and traffics to the nucleus, with the aid of the dynein motor protein. Together, these data suggest that microtubules are critically involved in the nuclear trafficking and transcriptional activity of HIF-1α. We also show that the connection between the microtubule cytoskeleton and HIF-1α regulation is lost in renal cell carcinoma (RCC), where HIF-1α is overexpressed because of mutations in the von Hippel Lindau (VHL) tumor suppressor protein. Specifically, we show that MTD treatment of RCC cells did not impair HIF-1α nuclear accumulation or transcriptional activity, and had no effect on the polysome association profile of HIF-1α. Interestingly, we found that HIF-1α protein did not bind microtubules in RCC. Moreover, restoration of VHL function failed to restore the ability of MTDs to inhibit HIF-1α, suggesting that VHL does not contribute to this phenotype. Together, these results suggest that HIF-1α regulation is microtubule-independent, and likely contributes to the chemoresistant nature of RCCs. Further understanding of the microtubule-dependent HIF-1α regulation, and lack thereof in RCC, is essential given the importance of HIF-1α in tumor biology, and the widespread use of MTDs in clinical oncology. Disruption of the microtubule cytoskeleton impairs tumor angiogenesis by inhibiting the hypoxia-inducible factor (HIF-1α) pathway. However, the signaling cascade linking microtubule disruption to HIF-1α inactivation has not been elucidated. Here, we show that microtubule-targeting drug (MTD) treatment impaired HIF-1α protein nuclear translocation, which significantly down-regulated HIF transcriptional activity. We provide strong evidence that HIF-1α protein associates with polymerized microtubules and traffics to the nucleus, with the aid of the dynein motor protein. Together, these data suggest that microtubules are critically involved in the nuclear trafficking and transcriptional activity of HIF-1α. We also show that the connection between the microtubule cytoskeleton and HIF-1α regulation is lost in renal cell carcinoma (RCC), where HIF-1α is overexpressed because of mutations in the von Hippel Lindau (VHL) tumor suppressor protein. Specifically, we show that MTD treatment of RCC cells did not impair HIF-1α nuclear accumulation or transcriptional activity, and had no effect on the polysome association profile of HIF-1α. Interestingly, we found that HIF-1α protein did not bind microtubules in RCC. Moreover, restoration of VHL function failed to restore the ability of MTDs to inhibit HIF-1α, suggesting that VHL does not contribute to this phenotype. Together, these results suggest that HIF-1α regulation is microtubule-independent, and likely contributes to the chemoresistant nature of RCCs. Further understanding of the microtubule-dependent HIF-1α regulation, and lack thereof in RCC, is essential given the importance of HIF-1α in tumor biology, and the widespread use of MTDs in clinical oncology." @default.
• W2160086543 created "2016-06-24" @default.
• W2160086543 creator A5003397614 @default.
• W2160086543 creator A5030164649 @default.
• W2160086543 creator A5063689745 @default.
• W2160086543 creator A5071742061 @default.
• W2160086543 creator A5071996306 @default.
• W2160086543 date "2012-04-01" @default.
• W2160086543 modified "2023-10-04" @default.
• W2160086543 title "Microtubules Regulate Hypoxia-inducible Factor-1α Protein Trafficking and Activity" @default.
• W2160086543 cites W1527191068 @default.
• W2160086543 cites W1588942504 @default.
• W2160086543 cites W1966051760 @default.
• W2160086543 cites W1981124017 @default.
• W2160086543 cites W1996491270 @default.
• W2160086543 cites W2011810742 @default.
• W2160086543 cites W2023952710 @default.
• W2160086543 cites W2035908704 @default.
• W2160086543 cites W2041881143 @default.
• W2160086543 cites W2042145670 @default.
• W2160086543 cites W2048454522 @default.
• W2160086543 cites W2048464939 @default.
• W2160086543 cites W2049413879 @default.
• W2160086543 cites W2049970665 @default.
• W2160086543 cites W2057963096 @default.
• W2160086543 cites W2060764929 @default.
• W2160086543 cites W2068091544 @default.
• W2160086543 cites W2073162690 @default.
• W2160086543 cites W2074888950 @default.
• W2160086543 cites W2076844582 @default.
• W2160086543 cites W2081252249 @default.
• W2160086543 cites W2088972647 @default.
• W2160086543 cites W2098811095 @default.
• W2160086543 cites W2110956743 @default.
• W2160086543 cites W2114480016 @default.
• W2160086543 cites W2115850825 @default.
• W2160086543 cites W2120863112 @default.
• W2160086543 cites W2123629153 @default.
• W2160086543 cites W2127868482 @default.
• W2160086543 cites W2129053861 @default.
• W2160086543 cites W2131544701 @default.
• W2160086543 cites W2134983040 @default.
• W2160086543 cites W2140834763 @default.
• W2160086543 cites W2143643440 @default.
• W2160086543 cites W2151285111 @default.
• W2160086543 cites W2154603906 @default.
• W2160086543 cites W2157031202 @default.
• W2160086543 cites W2159965729 @default.
• W2160086543 cites W2161216917 @default.
• W2160086543 cites W2166435019 @default.
• W2160086543 cites W2171230661 @default.
• W2160086543 cites W2171256437 @default.
• W2160086543 cites W2313701767 @default.
• W2160086543 doi "https://doi.org/10.1074/jbc.m112.345587" @default.
• W2160086543 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3320934" @default.
• W2160086543 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22367210" @default.
• W2160086543 hasPublicationYear "2012" @default.
• W2160086543 type Work @default.
• W2160086543 sameAs 2160086543 @default.
• W2160086543 citedByCount "57" @default.
• W2160086543 countsByYear W21600865432012 @default.
• W2160086543 countsByYear W21600865432013 @default.
• W2160086543 countsByYear W21600865432014 @default.
• W2160086543 countsByYear W21600865432015 @default.
• W2160086543 countsByYear W21600865432016 @default.
• W2160086543 countsByYear W21600865432017 @default.
• W2160086543 countsByYear W21600865432018 @default.
• W2160086543 countsByYear W21600865432019 @default.
• W2160086543 countsByYear W21600865432020 @default.
• W2160086543 countsByYear W21600865432021 @default.
• W2160086543 countsByYear W21600865432022 @default.
• W2160086543 countsByYear W21600865432023 @default.
• W2160086543 crossrefType "journal-article" @default.
• W2160086543 hasAuthorship W2160086543A5003397614 @default.
• W2160086543 hasAuthorship W2160086543A5030164649 @default.
• W2160086543 hasAuthorship W2160086543A5063689745 @default.
• W2160086543 hasAuthorship W2160086543A5071742061 @default.
• W2160086543 hasAuthorship W2160086543A5071996306 @default.
• W2160086543 hasBestOaLocation W21600865431 @default.
• W2160086543 hasConcept C104317684 @default.
• W2160086543 hasConcept C20418707 @default.
• W2160086543 hasConcept C54355233 @default.
• W2160086543 hasConcept C86339819 @default.
• W2160086543 hasConcept C86803240 @default.
• W2160086543 hasConcept C95444343 @default.
• W2160086543 hasConceptScore W2160086543C104317684 @default.
• W2160086543 hasConceptScore W2160086543C20418707 @default.
• W2160086543 hasConceptScore W2160086543C54355233 @default.
• W2160086543 hasConceptScore W2160086543C86339819 @default.
• W2160086543 hasConceptScore W2160086543C86803240 @default.
• W2160086543 hasConceptScore W2160086543C95444343 @default.
• W2160086543 hasIssue "15" @default.
• W2160086543 hasLocation W21600865431 @default.
• W2160086543 hasLocation W21600865432 @default.
• W2160086543 hasLocation W21600865433 @default.
• W2160086543 hasLocation W21600865434 @default.
• W2160086543 hasOpenAccess W2160086543 @default.
• W2160086543 hasPrimaryLocation W21600865431 @default.

• next