Insights into The Function and Regulation of Jumonji C Lysine Demethylases as Hypoxic Responsive Enzymes

Anand       Chopra; Hemanta       Adhikary; William    G.    Willmore; Kyle    K.    Biggar
doi:10.2174/1389203721666191231104225
Abstract

Cellular responses to hypoxia (low oxygen) are governed by oxygen sensitive signaling pathways. Such pathways, in part, are controlled by enzymes with oxygen-dependent catalytic activity, of which the role of prolyl 4-hydroxylases has been widely reviewed. These enzymes inhibit hypoxic response by inducing the oxygen-dependent degradation of hypoxia-inducible factor 1α, the master regulator of the transcriptional hypoxic response. Jumonji C domain-containing lysine demethylases are similar enzymes which share the same oxygen-dependent catalytic mechanism as prolyl 4- hydroxylases. Traditionally, the role of lysine demethylases has been studied in relation to demethylation activity against histone substrates, however, within the past decade an increasing number of nonhistone protein targets have been revealed, some of which have a key role in survival in the hypoxic tumor microenvironment. Within this review, we highlight the involvement of methyllysine in the hypoxic response with a focus on the HIF signaling pathway, the regulation of demethylase activity by oxygen, and provide insights into notable areas of future hypoxic demethylase research.
Keywords: Hypoxia, hypoxia-inducible factor, methyllysine, lysine demethylase, Jumonji C, non-histone, hypoxic signaling, oxygen affinity.
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DOI https://dx.doi.org/10.2174/1389203721666191231104225	Print ISSN 1389-2037
Publisher Name Bentham Science Publisher	Online ISSN 1875-5550
Current Protein & Peptide Science

Insights into The Function and Regulation of Jumonji C Lysine Demethylases as Hypoxic Responsive Enzymes

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