Substrate-Trapped Interactors of PHD3 and FIH Cluster in Distinct Signaling Pathways
Files in This Item:
|Substrate-Trapped Interactors of PHD3 and FIH Cluster.. GarciaA & TaylorC.pdf||4.74 MB||Adobe PDF||Download|
|Title:||Substrate-Trapped Interactors of PHD3 and FIH Cluster in Distinct Signaling Pathways||Authors:||Rodriguez, Javier
Garcia Munoz, Amaya
Nguyen, Lan K.
Kennedy, Susan A.
Taylor, Cormac T.
Kriegsheim, Alexander von
|Permanent link:||http://hdl.handle.net/10197/9754||Date:||22-Mar-2016||Online since:||2019-04-01T09:58:06Z||Abstract:||Amino acid hydroxylation is a post-translational modification that regulates intra- and inter-molecular protein-protein interactions. The modifications are regulated by a family of 2-oxoglutarate- (2OG) dependent enzymes and, although the biochemistry is well understood, until now only a few substrates have been described for these enzymes. Using quantitative interaction proteomics, we screened for substrates of the proline hydroxylase PHD3 and the asparagine hydroxylase FIH, which regulate the HIF-mediated hypoxic response. We were able to identify hundreds of potential substrates. Enrichment analysis revealed that the potential substrates of both hydroxylases cluster in the same pathways but frequently modify different nodes of signaling networks. We confirm that two proteins identified in our screen, MAPK6 (Erk3) and RIPK4, are indeed hydroxylated in a FIH- or PHD3-dependent mechanism. We further determined that FIH-dependent hydroxylation regulates RIPK4-dependent Wnt signaling, and that PHD3-dependent hydroxylation of MAPK6 protects the protein from proteasomal degradation.||Funding Details:||European Commission - Seventh Framework Programme (FP7)
Science Foundation Ireland
University College Dublin
|Type of material:||Journal Article||Publisher:||Elsevier||Journal:||Cell Reports||Volume:||14||Issue:||11||Start page:||2745||End page:||2760||Copyright (published version):||2016 the Authors||Keywords:||Hypoxiaregulated pathways; FIH; RIPK4 kinase activity; Hyroxylation; PHD3; MAPk6; Erk3; Quantitative interaction proteomics; Cellular functions; Direct hydroxylation||DOI:||10.1016/j.celrep.2016.02.043||Language:||en||Status of Item:||Peer reviewed|
|Appears in Collections:||SBI Research Collection|
Show full item record
This item is available under the Attribution-NonCommercial-NoDerivs 3.0 Ireland. No item may be reproduced for commercial purposes. For other possible restrictions on use please refer to the publisher's URL where this is made available, or to notes contained in the item itself. Other terms may apply.