Hydroxylation of the acetyltransferase NAA10 Trp38 is not an enzyme-switch in human cells

Rasmus Ree; Karoline Krogstad; Nina McTiernan; Magnus E. Jakobsson; Thomas Arnesen

doi:10.3390/ijms222111805

Hydroxylation of the acetyltransferase NAA10 Trp38 is not an enzyme-switch in human cells

Rasmus Ree, Karoline Krogstad, Nina McTiernan, Magnus E. Jakobsson, Thomas Arnesen

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Abstract

NAA10 is a major N-terminal acetyltransferase (NAT) that catalyzes the cotranslational N-terminal (Nt-) acetylation of 40% of the human proteome. Several reports of lysine acetyltransferase (KAT) activity by NAA10 exist, but others have not been able to find any NAA10-derived KAT activity, the latter of which is supported by structural studies. The KAT activity of NAA10 towards hypoxia-inducible factor 1α (HIF-1α) was recently found to depend on the hydroxylation at Trp38 of NAA10 by factor inhibiting HIF-1α (FIH). In contrast, we could not detect hydroxylation of Trp38 of NAA10 in several human cell lines and found no evidence that NAA10 interacts with or is regulated by FIH. Our data suggest that NAA10 Trp38 hydroxylation is not a switch in human cells and that it alters its catalytic activity from a NAT to a KAT.

Original language	English
Article number	11805
Journal	International Journal of Molecular Sciences
Volume	22
Issue number	21
DOIs	https://doi.org/10.3390/ijms222111805
Publication status	Published - 2021 Nov 1

Subject classification (UKÄ)

Medical Biotechnology

Free keywords

N-terminal acetyltransferase
NAA10
POST-translational modification
Protein acetylation
Protein hydroxylation
Proteomics

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title = "Hydroxylation of the acetyltransferase NAA10 Trp38 is not an enzyme-switch in human cells",

abstract = "NAA10 is a major N-terminal acetyltransferase (NAT) that catalyzes the cotranslational N-terminal (Nt-) acetylation of 40% of the human proteome. Several reports of lysine acetyltransferase (KAT) activity by NAA10 exist, but others have not been able to find any NAA10-derived KAT activity, the latter of which is supported by structural studies. The KAT activity of NAA10 towards hypoxia-inducible factor 1α (HIF-1α) was recently found to depend on the hydroxylation at Trp38 of NAA10 by factor inhibiting HIF-1α (FIH). In contrast, we could not detect hydroxylation of Trp38 of NAA10 in several human cell lines and found no evidence that NAA10 interacts with or is regulated by FIH. Our data suggest that NAA10 Trp38 hydroxylation is not a switch in human cells and that it alters its catalytic activity from a NAT to a KAT.",

keywords = "N-terminal acetyltransferase, NAA10, POST-translational modification, Protein acetylation, Protein hydroxylation, Proteomics",

author = "Rasmus Ree and Karoline Krogstad and Nina McTiernan and Jakobsson, {Magnus E.} and Thomas Arnesen",

note = "Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

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doi = "10.3390/ijms222111805",

language = "English",

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T1 - Hydroxylation of the acetyltransferase NAA10 Trp38 is not an enzyme-switch in human cells

AU - Ree, Rasmus

AU - Krogstad, Karoline

AU - McTiernan, Nina

AU - Jakobsson, Magnus E.

AU - Arnesen, Thomas

PY - 2021/11/1

Y1 - 2021/11/1

N2 - NAA10 is a major N-terminal acetyltransferase (NAT) that catalyzes the cotranslational N-terminal (Nt-) acetylation of 40% of the human proteome. Several reports of lysine acetyltransferase (KAT) activity by NAA10 exist, but others have not been able to find any NAA10-derived KAT activity, the latter of which is supported by structural studies. The KAT activity of NAA10 towards hypoxia-inducible factor 1α (HIF-1α) was recently found to depend on the hydroxylation at Trp38 of NAA10 by factor inhibiting HIF-1α (FIH). In contrast, we could not detect hydroxylation of Trp38 of NAA10 in several human cell lines and found no evidence that NAA10 interacts with or is regulated by FIH. Our data suggest that NAA10 Trp38 hydroxylation is not a switch in human cells and that it alters its catalytic activity from a NAT to a KAT.

AB - NAA10 is a major N-terminal acetyltransferase (NAT) that catalyzes the cotranslational N-terminal (Nt-) acetylation of 40% of the human proteome. Several reports of lysine acetyltransferase (KAT) activity by NAA10 exist, but others have not been able to find any NAA10-derived KAT activity, the latter of which is supported by structural studies. The KAT activity of NAA10 towards hypoxia-inducible factor 1α (HIF-1α) was recently found to depend on the hydroxylation at Trp38 of NAA10 by factor inhibiting HIF-1α (FIH). In contrast, we could not detect hydroxylation of Trp38 of NAA10 in several human cell lines and found no evidence that NAA10 interacts with or is regulated by FIH. Our data suggest that NAA10 Trp38 hydroxylation is not a switch in human cells and that it alters its catalytic activity from a NAT to a KAT.

KW - N-terminal acetyltransferase

KW - NAA10

KW - POST-translational modification

KW - Protein acetylation

KW - Protein hydroxylation

KW - Proteomics

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DO - 10.3390/ijms222111805

M3 - Article

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AN - SCOPUS:85118114250

SN - 1661-6596

VL - 22

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

IS - 21

M1 - 11805

ER -

Hydroxylation of the acetyltransferase NAA10 Trp38 is not an enzyme-switch in human cells

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