Casein kinase 1 regulates human hypoxia-inducible factor HIF-1
| dc.contributor.author | Kalousi, A. | en |
| dc.contributor.author | Mylonis, I. | en |
| dc.contributor.author | Politou, A. S. | en |
| dc.contributor.author | Chachami, G. | en |
| dc.contributor.author | Paraskeva, E. | en |
| dc.contributor.author | Simos, G. | en |
| dc.date.accessioned | 2015-11-24T19:31:29Z | |
| dc.date.available | 2015-11-24T19:31:29Z | |
| dc.identifier.issn | 1477-9137 | - |
| dc.identifier.uri | https://olympias.lib.uoi.gr/jspui/handle/123456789/23273 | |
| dc.rights | Default Licence | - |
| dc.subject | Amino Acid Sequence | en |
| dc.subject | Casein Kinase Idelta/genetics/*metabolism | en |
| dc.subject | Cell Hypoxia/physiology | en |
| dc.subject | HEK293 Cells | en |
| dc.subject | HeLa Cells | en |
| dc.subject | Humans | en |
| dc.subject | Hypoxia-Inducible Factor 1/genetics/*metabolism | en |
| dc.subject | Hypoxia-Inducible Factor 1, alpha Subunit/metabolism | en |
| dc.subject | Models, Molecular | en |
| dc.subject | Molecular Sequence Data | en |
| dc.subject | Nuclear Proteins/genetics/metabolism | en |
| dc.subject | Phosphorylation | en |
| dc.subject | Transcription Factors/genetics/metabolism | en |
| dc.subject | Transcriptional Activation | en |
| dc.title | Casein kinase 1 regulates human hypoxia-inducible factor HIF-1 | en |
| heal.abstract | Hypoxia-inducible factor 1 (HIF-1), a transcriptional activator that mediates cellular response to hypoxia and a promising target of anticancer therapy, is essential for adaptation to low oxygen conditions, embryogenesis and tumor progression. HIF-1 is a heterodimer of HIF-1alpha, expression of which is controlled by oxygen levels as well as by various oxygen-independent mechanisms, and HIF-1beta (or ARNT), which is constitutively expressed. In this work, we investigate the phosphorylation of the N-terminal heterodimerization (PAS) domain of HIF-1alpha and identify Ser247 as a major site of in vitro modification by casein kinase 1delta (CK1delta). Mutation of this site to alanine, surprisingly, enhanced the transcriptional activity of HIF-1alpha, a result phenocopied by inhibition or small interfering RNA (siRNA)-mediated silencing of CK1delta under hypoxic conditions. Conversely, overexpression of CK1delta or phosphomimetic mutation of Ser247 to aspartate inhibited HIF-1alpha activity without affecting its stability or nuclear accumulation. Immunoprecipitation and in vitro binding experiments suggest that CK1-dependent phosphorylation of HIF-1alpha at Ser247 impairs its association with ARNT, a notion also supported by modeling the structure of the complex between HIF-1alpha and ARNT PAS-B domains. We suggest that modification of HIF-1alpha by CK1 represents a novel mechanism that controls the activity of HIF-1 during hypoxia by regulating the interaction between its two subunits. | en |
| heal.access | campus | - |
| heal.fullTextAvailability | TRUE | - |
| heal.identifier.primary | 10.1242/jcs.068122 | - |
| heal.identifier.secondary | http://www.ncbi.nlm.nih.gov/pubmed/20699359 | - |
| heal.identifier.secondary | http://jcs.biologists.org/content/123/17/2976.full.pdf | - |
| heal.journalName | J Cell Sci | en |
| heal.journalType | peer-reviewed | - |
| heal.language | en | - |
| heal.publicationDate | 2010 | - |
| heal.recordProvider | Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής | el |
| heal.type | journalArticle | - |
| heal.type.el | Άρθρο Περιοδικού | el |
| heal.type.en | Journal article | en |
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