2-Oxoglutarate-dependent dioxygenases in cancer
|Author:||Losman, Julie-Aurore1,2; Koivunen, Peppi3; Kaelin, Jr., William G.1,4|
1Department of Medical Oncology, Dana-Farber Cancer Institute and Brigham and Women’s Hospital, Boston, MA, USA
2Division of Hematology, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
3Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, Oulu Center for Cell-Matrix Research, University of Oulu, Oulu, Finland
4Howard Hughes Medical Institute (HHMI), Chevy Chase, MD, USA
|Online Access:||PDF Full Text (PDF, 1.3 MB)|
|Persistent link:|| http://urn.fi/urn:nbn:fi-fe202101121642
|Publish Date:|| 2021-04-21
2-Oxoglutarate-dependent dioxygenases (2OGDDs) are a superfamily of enzymes that play diverse roles in many biological processes, including regulation of hypoxia-inducible factor-mediated adaptation to hypoxia, extracellular matrix formation, epigenetic regulation of gene transcription and the reprogramming of cellular metabolism. 2OGDDs all require oxygen, reduced iron and 2-oxoglutarate (also known as α-ketoglutarate) to function, although their affinities for each of these co-substrates, and hence their sensitivity to depletion of specific co-substrates, varies widely. Numerous 2OGDDs are recurrently dysregulated in cancer. Moreover, cancer-specific metabolic changes, such as those that occur subsequent to mutations in the genes encoding succinate dehydrogenase, fumarate hydratase or isocitrate dehydrogenase, can dysregulate specific 2OGDDs. This latter observation suggests that the role of 2OGDDs in cancer extends beyond cancers that harbour mutations in the genes encoding members of the 2OGDD superfamily. Herein, we review the regulation of 2OGDDs in normal cells and how that regulation is corrupted in cancer.
Nature reviews. Cancer
|Pages:||710 - 726|
|Type of Publication:||
A2 Review article in a scientific journal
|Field of Science:||
This work was supported by Academy of Finland grants 266719 and 308009 and grants from the S. Jusélius Foundation, the Finnish Cancer Organization and the Jane and Aatos Erkko Foundation to P.K. J.-A.L. is supported by the NIH. W.G.K. is a Howard Hughes Medical Investigator and supported by the NIH.
|Academy of Finland Grant Number:||
266719 (Academy of Finland Funding decision)
308009 (Academy of Finland Funding decision)
© Springer Nature Limited 2020. This is a post-peer-review, pre-copyedit version of an article published in Nat Rev Cancer. The final authenticated version is available online at https://doi.org/10.1038/s41568-020-00303-3.