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HYPK promotes the activity of the N α -acetyltransferase A complex to determine proteostasis of nonAc-X 2 /N-degron–containing proteins
Science Advances ( IF 11.7 ) Pub Date : 2022-06-15 , DOI: 10.1126/sciadv.abn6153
Pavlína Miklánková 1 , Eric Linster 1 , Jean-Baptiste Boyer 2 , Jonas Weidenhausen 3 , Johannes Mueller 4 , Laura Armbruster 1 , Karine Lapouge 3 , Carolina De La Torre 5 , Willy Bienvenut 2 , Carsten Sticht 5 , Matthias Mann 4 , Thierry Meinnel 2 , Irmgard Sinning 3 , Carmela Giglione 2 , Rüdiger Hell 1 , Markus Wirtz 1
Affiliation  

In humans, the Huntingtin yeast partner K (HYPK) binds to the ribosome-associated N α -acetyltransferase A (NatA) complex that acetylates ~40% of the proteome in humans and Arabidopsis thaliana . However, the relevance of Hs HYPK for determining the human N-acetylome is unclear. Here, we identify the At HYPK protein as the first in vivo regulator of NatA activity in plants . At HYPK physically interacts with the ribosome-anchoring subunit of NatA and promotes N α -terminal acetylation of diverse NatA substrates. Loss-of- At HYPK mutants are remarkably resistant to drought stress and strongly resemble the phenotype of NatA-depleted plants. The ectopic expression of Hs HYPK 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-X 2 /N-degron. This N-degron targets many nonacetylated NatA substrates for degradation by the ubiquitin-proteasome system.

中文翻译:

HYPK 促进 N α -乙酰转移酶 A 复合物的活性以确定非Ac-X 2 /N-degron 含蛋白质的蛋白质稳态

在人类中,亨廷顿酵母伴侣 K (HYPK) 与核糖体相关ñ α-乙酰转移酶 A (NatA) 复合物,可乙酰化人类约 40% 的蛋白质组和拟南芥. 然而,相关性高铁用于确定人类 N-乙酰组的 HYPK 尚不清楚。在这里,我们确定HYPK 蛋白作为植物中 NatA 活性的第一个体内调节剂. 在HYPK 与 NatA 的核糖体锚定亚基物理相互作用并促进 Nα-不同NatA底物的末端乙酰化。丢失-HYPK 突变体对干旱胁迫具有显着的抵抗力,并且与 NatA 耗尽植物的表型非常相似。异位表达高铁HYPK 拯救了这种表型。结合转录组学、蛋白质组学和 N 端组学揭示 HYPK 主要通过调节 NatA 活性损害植物代谢和发育。我们通过促进掩盖最近发现的 nonAc-X 来证明 HYPK 是全球蛋白质稳态的关键调节剂2/N-degron。这种 N-degron 靶向许多非乙酰化 NatA 底物,以便被泛素-蛋白酶体系统降解。
更新日期:2022-06-15
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