Karttunen Sarah, Duffield Michael, Scrimgeour Nathan R, Squires Lauren, Lim Wai Li, Dallas Mark L, Scragg Jason L, Chicher Johana, Dave Keyur A, Whitelaw Murray L, Peers Chris, Gorman Jeffrey J, Gleadle Jonathan M, Rychkov Grigori Y, Peet Daniel J
@article{karttunen_oxygen-dependent_2015,
title = {Oxygen-dependent hydroxylation by FIH regulates the TRPV3 ion channel.},
author = {Sarah Karttunen and Michael Duffield and Nathan R Scrimgeour and Lauren Squires and Wai Li Lim and Mark L Dallas and Jason L Scragg and Johana Chicher and Keyur A Dave and Murray L Whitelaw and Chris Peers and Jeffrey J Gorman and Jonathan M Gleadle and Grigori Y Rychkov and Daniel J Peet},
doi = {10.1242/jcs.158451},
issn = {1477-9137 0021-9533},
year = {2015},
date = {2015-01-01},
journal = {Journal of cell science},
volume = {128},
number = {2},
pages = {225--231},
abstract = {Factor inhibiting HIF (FIH, also known as HIF1AN) is an oxygen-dependent asparaginyl hydroxylase that regulates the hypoxia-inducible factors (HIFs). Several proteins containing ankyrin repeat domains (ARDs) have been characterised as substrates of FIH, although there is little evidence for a functional consequence of hydroxylation on these substrates. This study demonstrates that the transient receptor potential vanilloid 3 (TRPV3) channel is hydroxylated by FIH on asparagine 242 within the cytoplasmic ARD. Hypoxia, FIH inhibitors and mutation of asparagine 242 all potentiated TRPV3-mediated current, without altering TRPV3 protein levels, indicating that oxygen-dependent hydroxylation inhibits TRPV3 activity. This novel mechanism of channel regulation by oxygen-dependent asparaginyl hydroxylation is likely to extend to other ion channels.},
note = {Place: England},
keywords = {alpha Subunit/genetics/*metabolism, Amino Acid Sequence, Ankyrin Repeat/genetics, Cell Hypoxia/*genetics, FIH, HEK293 Cells, Humans, Hydroxylation, Hydroxylation/genetics, Hypoxia, Hypoxia-Inducible Factor 1, Mixed Function Oxygenases/antagonists & inhibitors/genetics/*metabolism, Mutation, Oxygen/metabolism, PPSE, Protein Binding, Repressor Proteins/antagonists & inhibitors/genetics/*metabolism, TRPV Cation Channels/genetics/*metabolism, TRPV3},
pubstate = {published},
tppubtype = {article}
}
Factor inhibiting HIF (FIH, also known as HIF1AN) is an oxygen-dependent asparaginyl hydroxylase that regulates the hypoxia-inducible factors (HIFs). Several proteins containing ankyrin repeat domains (ARDs) have been characterised as substrates of FIH, although there is little evidence for a functional consequence of hydroxylation on these substrates. This study demonstrates that the transient receptor potential vanilloid 3 (TRPV3) channel is hydroxylated by FIH on asparagine 242 within the cytoplasmic ARD. Hypoxia, FIH inhibitors and mutation of asparagine 242 all potentiated TRPV3-mediated current, without altering TRPV3 protein levels, indicating that oxygen-dependent hydroxylation inhibits TRPV3 activity. This novel mechanism of channel regulation by oxygen-dependent asparaginyl hydroxylation is likely to extend to other ion channels.