Abstract
Amino acid hydroxylation is a common post-translational modification, which generally regulates protein interactions or adds a functional group that can be further modified. Such hydroxylation is currently considered irreversible, necessitating the degradation and re-synthesis of the entire protein to reset the modification. Here we present evidence that the cellular machinery can reverse FIH-mediated asparagine hydroxylation on intact proteins. These data suggest that asparagine hydroxylation is a flexible and dynamic post-translational modification akin to modifications involved in regulating signaling networks, such as phosphorylation, methylation and ubiquitylation.
Keywords:
Post-translational modifications; SILAC; affinity proteomics; factor-inhibiting-HIF; hydroxylation; mass spectrometry; signal transduction.
© 2020 Rodriguez et al.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Asparagine / metabolism*
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Cell Line, Tumor
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Humans
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Hydroxylation
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Hypoxia-Inducible Factor 1, alpha Subunit / genetics
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
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Kinetics
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Mass Spectrometry
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Methylation
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Mixed Function Oxygenases / genetics
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Mixed Function Oxygenases / metabolism*
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Phosphorylation
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Protein Binding
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Protein Processing, Post-Translational*
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Signal Transduction
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TRPV Cation Channels / genetics
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TRPV Cation Channels / metabolism*
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Tankyrases / genetics
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Tankyrases / metabolism*
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Ubiquitination
Substances
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HIF1A protein, human
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Hypoxia-Inducible Factor 1, alpha Subunit
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Repressor Proteins
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TRPV Cation Channels
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TRPV3 protein, human
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Asparagine
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Mixed Function Oxygenases
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HIF1AN protein, human
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TNKS2 protein, human
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Tankyrases