Proteomics

Dataset Information

245

PHD3 and FIH substrates cluster in distinct signalling pathways


ABSTRACT: Amino acid hydroxylation is a common post-translational modification which 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. We present here a sensitive method which specifically enriches and identifies hydroxylase substrates. We screened for substrates of PHD3 and FIH, a proline and asparagine hydroxylase respectively which regulate the HIF-mediated hypoxic response and were able to confirm known substrates as well as identifying hundreds of potential novel ones. Enrichment analysis revealed that the substrates of both hydroxylases cluster in the same pathways but frequently modify different nodes of these networks. We confirm that two proteins identified in this screen, MAPK6 and RIPK4, are indeed hydroxylated in a FIH or PHD3 dependent mechanism and explore the biological consequences of the hydroxylation.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo sapiens  

TISSUE(S): Tissue Not Applicable To Dataset

DISEASE(S): Not Available

SUBMITTER: Alex von kriegsheim  

LAB HEAD: Alex von Kriegsheim

PROVIDER: PXD001085 | Pride | 2016-03-30

REPOSITORIES: Pride

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Publications

Substrate-Trapped Interactors of PHD3 and FIH Cluster in Distinct Signaling Pathways.

Rodriguez Javier J   Pilkington Ruth R   Garcia Munoz Amaya A   Nguyen Lan K LK   Rauch Nora N   Kennedy Susan S   Monsefi Naser N   Herrero Ana A   Taylor Cormac T CT   von Kriegsheim Alex A  

Cell reports 20160310 11


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  ...[more]

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