BACKGROUND: The production of collagen is fundamental to atherosclerosis and critically dependent on posttranslational modification by prolyl 4-hydroxylase. METHODS AND RESULTS: We report the cloning of a novel prolyl 4-hydroxylase catalytic (alpha) subunit from human vascular smooth muscle cells. The peptide displayed conservation of critical residues for interacting with Fe2+ and 2-oxoglutarate, essential cosubstrates for prolyl 4-hydroxylase activity. Furthermore, when the recombinant protein was expressed in cells, it associated with the beta-subunit of prolyl 4-hydroxylase and could catalyze prolyl 4-hydroxylation of a collagen-like peptide. The tissue distribution was dissimilar from that of the 2 previously cloned alpha-subunits, suggesting a role beyond redundancy. Importantly, the novel gene was expressed in the fibrous cap of human carotid atherosclerotic lesions. CONCLUSIONS: The discovery of a novel prolyl 4-hydroxylase alpha-subunit, here termed the alpha(III)-subunit, suggests a new participant in collagen synthesis that, in view of the expression findings, may be relevant to atherosclerotic disease.
BACKGROUND: The production of collagen is fundamental to atherosclerosis and critically dependent on posttranslational modification by prolyl 4-hydroxylase. METHODS AND RESULTS: We report the cloning of a novel prolyl 4-hydroxylase catalytic (alpha) subunit from human vascular smooth muscle cells. The peptide displayed conservation of critical residues for interacting with Fe2+ and 2-oxoglutarate, essential cosubstrates for prolyl 4-hydroxylase activity. Furthermore, when the recombinant protein was expressed in cells, it associated with the beta-subunit of prolyl 4-hydroxylase and could catalyze prolyl 4-hydroxylation of a collagen-like peptide. The tissue distribution was dissimilar from that of the 2 previously cloned alpha-subunits, suggesting a role beyond redundancy. Importantly, the novel gene was expressed in the fibrous cap of human carotid atherosclerotic lesions. CONCLUSIONS: The discovery of a novel prolyl 4-hydroxylase alpha-subunit, here termed the alpha(III)-subunit, suggests a new participant in collagen synthesis that, in view of the expression findings, may be relevant to atherosclerotic disease.
Authors: Ellinoora Aro; Antti M Salo; Richa Khatri; Mikko Finnilä; Ilkka Miinalainen; Raija Sormunen; Outi Pakkanen; Tiina Holster; Raija Soininen; Carina Prein; Hauke Clausen-Schaumann; Attila Aszódi; Juha Tuukkanen; Kari I Kivirikko; Ernestina Schipani; Johanna Myllyharju Journal: J Biol Chem Date: 2015-05-22 Impact factor: 5.157
Authors: Yaqun Zou; Sandra Donkervoort; Antti M Salo; A Reghan Foley; Aileen M Barnes; Ying Hu; Elena Makareeva; Meganne E Leach; Payam Mohassel; Jahannaz Dastgir; Matthew A Deardorff; Ronald D Cohn; Wendy O DiNonno; Fransiska Malfait; Monkol Lek; Sergey Leikin; Joan C Marini; Johanna Myllyharju; Carsten G Bönnemann Journal: Hum Mol Genet Date: 2017-06-15 Impact factor: 6.150
Authors: Aithne Atkinson; Alexander Renziehausen; Hexiao Wang; Cristiana Lo Nigro; Laura Lattanzio; Marco Merlano; Bhavya Rao; Lynda Weir; Alan Evans; Rubeta Matin; Catherine Harwood; Peter Szlosarek; J Geoffrey Pickering; Colin Fleming; Van Ren Sim; Su Li; James T Vasta; Ronald T Raines; Mathieu Boniol; Alastair Thompson; Charlotte Proby; Tim Crook; Nelofer Syed Journal: J Invest Dermatol Date: 2018-11-16 Impact factor: 8.551