{"data":{"id":"10.6084/m9.figshare.1444403.v8","type":"dois","attributes":{"doi":"10.6084/m9.figshare.1444403.v8","prefix":"10.6084","suffix":"m9.figshare.1444403.v8","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Shuyang Chen","affiliation":[],"nameIdentifiers":[]},{"name":"Chengqian Yin","affiliation":[],"nameIdentifiers":[]},{"name":"Taotao Lao","affiliation":[],"nameIdentifiers":[]},{"name":"Dongming Liang","affiliation":[],"nameIdentifiers":[]},{"name":"He, Dan","nameType":"Personal","givenName":"Dan","familyName":"He","affiliation":[],"nameIdentifiers":[]},{"name":"Chenguang Wang","affiliation":[],"nameIdentifiers":[]},{"name":"Nianli Sang","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"AMPK-HDAC5 pathway facilitates nuclear accumulation of HIF-1α and functional activation of HIF-1 by deacetylating Hsp70 in the cytosol"}],"publisher":"Taylor \u0026 Francis","container":{},"publicationYear":2015,"subjects":[{"subject":"Biochemistry"},{"subject":"Cell Biology"},{"subject":"Genetics"},{"subject":"FOS: Biological sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Biological sciences","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Molecular Biology"},{"subject":"Physiology"},{"subject":"39999 Chemical Sciences not elsewhere classified","subjectScheme":"FOR"},{"subject":"FOS: Chemical sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Chemical sciences","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Immunology"},{"subject":"FOS: Clinical medicine","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"FOS: Clinical medicine","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Marine Biology"},{"subject":"Cancer"},{"subject":"Hematology"}],"contributors":[],"dates":[{"date":"2015-10-09","dateType":"Created"},{"date":"2019-06-03","dateType":"Updated"},{"date":"2015","dateType":"Issued"}],"language":null,"types":{"ris":"DATA","bibtex":"misc","citeproc":"dataset","schemaOrg":"Dataset","resourceType":"Dataset","resourceTypeGeneral":"Dataset"},"relatedIdentifiers":[{"relationType":"IsSupplementTo","relatedIdentifier":"10.1080/15384101.2015.1055426","relatedIdentifierType":"DOI"},{"relationType":"IsIdenticalTo","relatedIdentifier":"10.6084/m9.figshare.1444403","relatedIdentifierType":"DOI"}],"relatedItems":[],"sizes":["1135962 Bytes"],"formats":[],"version":null,"rightsList":[{"rights":"Creative Commons Attribution 4.0 International","rightsUri":"https://creativecommons.org/licenses/by/4.0/legalcode","schemeUri":"https://spdx.org/licenses/","rightsIdentifier":"cc-by-4.0","rightsIdentifierScheme":"SPDX"}],"descriptions":[{"description":"Hypoxia-inducible factor 1 (HIF-1) transcriptionally promotes production of adenosine triphosphate (ATP) whereas AMPK senses and regulates cellular energy homeostasis. A histone deacetylase (HDAC) activity has been proven to be critical for HIF-1 activation but the underlying mechanism and its role in energy homesostasis remain unclear. Here, we demonstrate that HIF-1 activation depends on a cytosolic, enzymatically active HDAC5. HDAC5 knockdown impairs hypoxia-induced HIF-1α accumulation and HIF-1 transactivation, whereas HDAC5 overexpression enhances HIF-1α stabilization and nuclear translocation. Mechanistically, we show that Hsp70 is a cytosolic substrate of HDAC5; and hyperacetylation renders Hsp70 higher affinity for HIF-1α binding, which correlates with accelerated degradation and attenuated nuclear accumulation of HIF-1α. Physiologically, AMPK-triggered cytosolic shuttling of HDAC5 is critical; inhibition of either AMPK or HDAC5 impairs HIF-1α nuclear accumulation under hypoxia or low glucose conditions. Finally, we show specifically suppressing HDAC5 is sufficient to inhibit tumor cell proliferation under hypoxic conditions. Our data delineate a novel link between AMPK, the energy sensor, and HIF-1, the major driver of ATP production, indicating that specifically inhibiting HDAC5 may selectively suppress the survival and proliferation of hypoxic tumor cells.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"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","url":"https://figshare.com/articles/AMPK_HDAC5_pathway_facilitates_nuclear_accumulation_of_HIF_1_945_and_functional_activation_of_HIF_1_by_deacetylating_Hsp70_in_the_cytosol/1444403/8","contentUrl":null,"metadataVersion":5,"schemaVersion":"http://datacite.org/schema/kernel-4","source":"mds","isActive":true,"state":"findable","reason":null,"viewCount":0,"viewsOverTime":[],"downloadCount":0,"downloadsOverTime":[],"referenceCount":0,"citationCount":0,"citationsOverTime":[],"partCount":0,"partOfCount":0,"versionCount":0,"versionOfCount":0,"created":"2016-01-19T22:58:54.000Z","registered":"2016-01-19T22:58:56.000Z","published":"2015","updated":"2020-09-04T17:04:22.000Z"},"relationships":{"client":{"data":{"id":"figshare.ars","type":"clients"}},"provider":{"data":{"id":"otjm","type":"providers"}},"media":{"data":{"id":"10.6084/m9.figshare.1444403.v8","type":"media"}},"references":{"data":[]},"citations":{"data":[]},"parts":{"data":[]},"partOf":{"data":[]},"versions":{"data":[]},"versionOf":{"data":[]}}}}