دورية أكاديمية
Substrate-Trapped Interactors of PHD3 and FIH Cluster in Distinct Signaling Pathways
| العنوان: | Substrate-Trapped Interactors of PHD3 and FIH Cluster in Distinct Signaling Pathways |
|---|---|
| المؤلفون: | Rodriguez, Javier, Pilkington, Ruth, Garcia Munoz, Amaya, Nguyen, Lan K., Rauch, Nora, Kennedy, Susan A., Monsefi, Naser, Herrero, Ana, Taylor, Cormac T., Kriegsheim, Alexander von |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2019 |
| المجموعة: | University College Dublin: Research Repository UCD |
| مصطلحات موضوعية: | Hypoxiaregulated pathways, FIH, RIPK4 kinase activity, Hyroxylation, PHD3, MAPk6, Erk3, Quantitative interaction proteomics, Cellular functions, Direct hydroxylation |
| الوصف: | 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. ; European Commission - Seventh Framework Programme (FP7) ; Science Foundation Ireland ; University College Dublin ; Cancer Research UK ; PRIMES Project |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | Cell Reports; http://hdl.handle.net/10197/9754Test; 14; 11; 2745; 2760; 06/ CE/B1129; 13/SIRG/2174; C157/A18075; FP7-HEALTH-2011-278568 |
| DOI: | 10.1016/j.celrep.2016.02.043 |
| الإتاحة: | https://doi.org/10.1016/j.celrep.2016.02.043Test http://hdl.handle.net/10197/9754Test |
| حقوق: | Published under a Creative Commons Attribution 4.0 International (CC BY 4.0) license. |
| رقم الانضمام: | edsbas.55A03327 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.celrep.2016.02.043 |
|---|