HYPK promotes the activity of the Nα-acetyltransferase A complex to determine proteostasis of nonAc-X2/N-degron-containing proteins
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HYPK promotes the activity of the Nα-acetyltransferase A complex to determine proteostasis of nonAc-X2/N-degron-containing proteins. / Miklánková, Pavlína; Linster, Eric; Boyer, Jean-Baptiste; Weidenhausen, Jonas; Mueller, Johannes; Armbruster, Laura; Lapouge, Karine; De La Torre, Carolina; Bienvenut, Willy; Sticht, Carsten; Mann, Matthias; Meinnel, Thierry; Sinning, Irmgard; Giglione, Carmela; Hell, Rüdiger; Wirtz, Markus.
In: Science Advances, Vol. 8, No. 24, eabn6153, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - HYPK promotes the activity of the Nα-acetyltransferase A complex to determine proteostasis of nonAc-X2/N-degron-containing proteins
AU - Miklánková, Pavlína
AU - Linster, Eric
AU - Boyer, Jean-Baptiste
AU - Weidenhausen, Jonas
AU - Mueller, Johannes
AU - Armbruster, Laura
AU - Lapouge, Karine
AU - De La Torre, Carolina
AU - Bienvenut, Willy
AU - Sticht, Carsten
AU - Mann, Matthias
AU - Meinnel, Thierry
AU - Sinning, Irmgard
AU - Giglione, Carmela
AU - Hell, Rüdiger
AU - Wirtz, Markus
PY - 2022
Y1 - 2022
N2 - In humans, the Huntingtin yeast partner K (HYPK) binds to the ribosome-associated Nα-acetyltransferase A (NatA) complex that acetylates ~40% of the proteome in humans and Arabidopsis thaliana. However, the relevance of HsHYPK for determining the human N-acetylome is unclear. Here, we identify the AtHYPK protein as the first in vivo regulator of NatA activity in plants. AtHYPK physically interacts with the ribosome-anchoring subunit of NatA and promotes Nα-terminal acetylation of diverse NatA substrates. Loss-of-AtHYPK mutants are remarkably resistant to drought stress and strongly resemble the phenotype of NatA-depleted plants. The ectopic expression of HsHYPK rescues this phenotype. Combined transcriptomics, proteomics, and N-terminomics unravel that HYPK impairs plant metabolism and development, predominantly by regulating NatA activity. We demonstrate that HYPK is a critical regulator of global proteostasis by facilitating masking of the recently identified nonAc-X2/N-degron. This N-degron targets many nonacetylated NatA substrates for degradation by the ubiquitin-proteasome system.
AB - In humans, the Huntingtin yeast partner K (HYPK) binds to the ribosome-associated Nα-acetyltransferase A (NatA) complex that acetylates ~40% of the proteome in humans and Arabidopsis thaliana. However, the relevance of HsHYPK for determining the human N-acetylome is unclear. Here, we identify the AtHYPK protein as the first in vivo regulator of NatA activity in plants. AtHYPK physically interacts with the ribosome-anchoring subunit of NatA and promotes Nα-terminal acetylation of diverse NatA substrates. Loss-of-AtHYPK mutants are remarkably resistant to drought stress and strongly resemble the phenotype of NatA-depleted plants. The ectopic expression of HsHYPK rescues this phenotype. Combined transcriptomics, proteomics, and N-terminomics unravel that HYPK impairs plant metabolism and development, predominantly by regulating NatA activity. We demonstrate that HYPK is a critical regulator of global proteostasis by facilitating masking of the recently identified nonAc-X2/N-degron. This N-degron targets many nonacetylated NatA substrates for degradation by the ubiquitin-proteasome system.
KW - Acetylation
KW - Acetyltransferases/metabolism
KW - Arabidopsis/genetics
KW - N-Terminal Acetyltransferase A/genetics
KW - N-Terminal Acetyltransferase E/genetics
KW - Proteostasis
U2 - 10.1126/sciadv.abn6153
DO - 10.1126/sciadv.abn6153
M3 - Journal article
C2 - 35704578
VL - 8
JO - Science advances
JF - Science advances
SN - 2375-2548
IS - 24
M1 - eabn6153
ER -
ID: 321783407