![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
2MB |
![[thumbnail of Supporting Information]](https://mdc-test.eprints-hosting.org/style/images/fileicons/application_pdf.png) |
PDF (Supporting Information)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
24MB |
| Item Type: | Article |
|---|---|
| Title: | Widespread hydroxylation of unstructured lysine-rich protein domains by JMJD6 |
| Creators Name: | Cockman, M.E., Sugimoto, Y., Pegg, H.B., Masson, N., Salah, E., Tumber, A., Flynn, H.R., Kirkpatrick, J.M., Schofield, C.J. and Ratcliffe, P.J. |
| Abstract: | The Jumonji domain-containing protein JMJD6 is a 2-oxoglutarate-dependent dioxygenase associated with a broad range of biological functions. Cellular studies have implicated the enzyme in chromatin biology, transcription, DNA repair, mRNA splicing, and cotranscriptional processing. Although not all studies agree, JMJD6 has been reported to catalyze both hydroxylation of lysine residues and demethylation of arginine residues. However, despite extensive study and indirect evidence for JMJD6 catalysis in many cellular processes, direct assignment of JMJD6 catalytic substrates has been limited. Examination of a reported site of proline hydroxylation within a lysine-rich region of the tandem bromodomain protein BRD4 led us to conclude that hydroxylation was in fact on lysine and catalyzed by JMJD6. This prompted a wider search for JMJD6-catalyzed protein modifications deploying mass spectrometric methods designed to improve the analysis of such lysine-rich regions. Using lysine derivatization with propionic anhydride to improve the analysis of tryptic peptides and nontryptic proteolysis, we report 150 sites of JMJD6-catalyzed lysine hydroxylation on 48 protein substrates, including 19 sites of hydroxylation on BRD4. Most hydroxylations were within lysine-rich regions that are predicted to be unstructured; in some, multiple modifications were observed on adjacent lysine residues. Almost all of the JMJD6 substrates defined in these studies have been associated with membraneless organelle formation. Given the reported roles of lysine-rich regions in subcellular partitioning by liquid-liquid phase separation, our findings raise the possibility that JMJD6 may play a role in regulating such processes in response to stresses, including hypoxia. |
| Keywords: | JMJD6, Lysine Hydroxylation, Lysine-Rich Domain, 2-Oxoglutarate-Dependent Dioxygenase, Hypoxia |
| Source: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Volume: | 119 |
| Number: | 32 |
| Page Range: | e2201483119 |
| Date: | 9 August 2022 |
| Official Publication: | https://doi.org/10.1073/pnas.2201483119 |
| PubMed: | View item in PubMed |
Repository Staff Only: item control page
