title: The HIF prolyl hydroxylase PHD3 is a potential substrate of the TRiC chaperonin.
abstract: Hypoxia-inducible factor-1 (HIF) is regulated by oxygen-dependent prolyl hydroxylation. Of the three HIF prolyl hydroxylases (PHD1, 2 and 3) identified, PHD3 exhibits restricted substrate specificity in vitro and is induced in different cell types by diverse stimuli. PHD3 may therefore provide an interface between oxygen sensing and other signalling pathways. We have used co-purification and mass spectrometry to identify proteins that interact with PHD3. The cytosolic chaperonin TRiC was found to copurify with PHD3 in extracts from several cell types. Our results indicate that PHD3 is a TRiC substrate, providing another step at which PHD3 activity may be regulated.
authors.affiliation: The Henry Wellcome Building of Genomic Medicine, Roosevelt Drive, Oxford OX3 7BN, UK.
authors.forename: Norma
authors.initials: N
authors.lastname: Masson
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Appelhoff
authors.forename: Jason R
authors.initials: JR
authors.lastname: Tuckerman
authors.forename: Ya-Min
authors.initials: YM
authors.lastname: Tian
authors.forename: Hans
authors.initials: H
authors.lastname: Demol
authors.forename: Magda
authors.initials: M
authors.lastname: Puype
authors.forename: Joel
authors.initials: J
authors.lastname: Vandekerckhove
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Ratcliffe
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Pugh
mesh_terms: D000465:Algorithms; D002460:Cell Line; D018833:Chaperonins / Q000737:chemistry*; D003600:Cytosol / Q000378:metabolism; D049308:Dioxygenases; D004492:Edetic Acid / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D000860:Hypoxia; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D015151:Immunoblotting; D010100:Oxygen / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011233:Precipitin Tests; D011393:Procollagen-Proline Dioxygenase / Q000737:chemistry* / Q000502:physiology*; D011485:Protein Binding; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012156:Reticulocytes / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014162:Transfection; D014357:Trypsin / Q000737:chemistry
chemical_list: D010455:Peptides; D004492:Edetic Acid; D049308:Dioxygenases; D011393:Procollagen-Proline Dioxygenase; C488894:EGLN3 protein, human; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D014357:Trypsin; D018833:Chaperonins; D010100:Oxygen