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Non-heme dioxygenases: cellular sensors and regulators jelly rolled into one?

Nature Chemical Biology volume 3, pages 144–153 (2007)Cite this article

Abstract

Members of the Fe(II)- and 2-oxoglutarate–dependent family of dioxygenases have long been known to oxidize several amino acids in various protein targets to facilitate protein folding. However, in recent years investigators have characterized several such hydroxylation modifications that serve a regulatory, rather than structural, purpose. Furthermore, the responsible enzymes seem to function directly as sensors of the cellular environment and metabolic state. For example, a cellular response pathway to low oxygen (hypoxia) is orchestrated through the actions of prolyl and asparaginyl hydroxylases that govern both the oxygen-dependent stability and transcriptional activity of the hypoxia-inducible transcription factor. Recently, a different subfamily of Fe(II)- and 2-oxoglutarate–dependent dioxygenases has been shown to carry out histone demethylation. The discovery of protein regulation via hydroxylation raises the possibility that other Fe(II)- and 2-oxoglutarate–dependent dioxygenases might also serve in a similar capacity.

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Figure 1: Protein hydroxylation by Fe(II)- and 2-oxoglutarate–dependent dioxygenases.
Figure 2: Regulation of the mammalian hypoxia response pathway.
Figure 3: HIF-α hydroxylation mediates interactions with pVHL and p300.
Figure 4: Structures of HIF prolyl (HPH-2/PHD2/EGLN1) and asparaginyl (FIH-1) hydroxylases.
Figure 5: Structure of the JmjC domain from the histone demethylase JHDM3A.

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Acknowledgements

R.K.B. is the Michael L. Rosenberg Scholar in Medical Research and is supported by awards from the Burroughs Wellcome Fund and the Welch Foundation. We thank J. Ready for helpful comments.

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  1. Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, 75390-9038, Texas, USA

    Abdullah Ozer & Richard K Bruick

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  1. Abdullah Ozer
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  2. Richard K Bruick
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Correspondence to Richard K Bruick.

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Ozer, A., Bruick, R. Non-heme dioxygenases: cellular sensors and regulators jelly rolled into one?. Nat Chem Biol 3, 144–153 (2007). https://doi.org/10.1038/nchembio863

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