Up-regulation of ubiquitin–proteasome activity upon loss of NatA-dependent N-terminal acetylation

Ilia Kats; Christian Reinbold; Marc Kschonsak; Anton Khmelinskii; Laura Armbruster; Thomas Ruppert; Michael Knop

doi:10.26508/lsa.202000730

journal article Open Access Nov 11, 2021

Up-regulation of ubiquitin–proteasome activity upon loss of NatA-dependent N-terminal acetylation

Ilia Kats

Christian Reinbold Marc Kschonsak

Anton Khmelinskii Laura Armbruster Thomas Ruppert

Michael Knop

Life Science Alliance Vol. 5 No. 2 pp. e202000730 · Life Science Alliance, LLC

View at Publisher Save 10.26508/lsa.202000730

Abstract

N-terminal acetylation is a prominent protein modification, and inactivation of N-terminal acetyltransferases (NATs) cause protein homeostasis stress. Using multiplexed protein stability profiling with linear ubiquitin fusions as reporters for the activity of the ubiquitin proteasome system, we observed increased ubiquitin proteasome system activity in NatA, but not NatB or NatC mutants. We find several mechanisms contributing to this behavior. First, NatA-mediated acetylation of the N-terminal ubiquitin–independent degron regulates the abundance of Rpn4, the master regulator of the expression of proteasomal genes. Second, the abundance of several E3 ligases involved in degradation of UFD substrates is increased in cells lacking NatA. Finally, we identify the E3 ligase Tom1 as a novel chain-elongating enzyme (E4) involved in the degradation of linear ubiquitin fusions via the formation of branched K11, K29, and K48 ubiquitin chains, independently of the known E4 ligases involved in UFD, leading to enhanced ubiquitination of the UFD substrates.

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References

87

[1]

10.1016/j.tibs.2016.07.005

[2]

A Statistical Model for Identifying Proteins by Tandem Mass Spectrometry

Alexey I. Nesvizhskii, Andrew Keller, Eugene Kolker et al.

Analytical Chemistry 10.1021/ac0341261

[3]

10.1016/j.bbamcr.2004.10.003

[4]

10.1128/mcb.00539-12

[5]

10.1126/science.3018930

[6]

The degradation signal in a short-lived protein

Andreas Bachmair, Alexander Varshavsky

Cell 10.1016/0092-8674(89)90635-1

[7]

10.1016/s0092-8674(03)00755-4

[8]

10.1002/bies.20210

[9]

10.1002/0471142727.mb1312s23

[10]

10.1128/mcb.24.14.6140-6150.2004

[11]

MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification

Jürgen Cox, Matthias Mann

Nature Biotechnology 10.1038/nbt.1511

[12]

10.1038/75406

[13]

10.1038/cdd.2011.16

[14]

Cdc48-associated complex bound to 60S particles is required for the clearance of aberrant translation products

Quentin Defenouillère, Yanhua Yao, John Mouaikel et al.

Proceedings of the National Academy of Sciences 10.1073/pnas.1221724110

[15]

10.1016/s0021-9258(19)74245-8

[16]

10.1074/jbc.m113.469726

[17]

10.1016/j.molcel.2013.06.004

[18]

The Ubiquitin–Proteasome System of Saccharomyces cerevisiae

Daniel Finley, Helle D Ulrich, Thomas Sommer et al.

Genetics 10.1534/genetics.112.140467

[19]

10.1016/j.celrep.2021.108711

[20]

10.15252/msb.20156662

[21]

10.1038/nature09816

[22]

The structure of the chromophore within DsRed, a red fluorescent protein from coral

Larry A. Gross, Geoffrey S. Baird, Ross C. Hoffman et al.

Proceedings of the National Academy of Sciences 10.1073/pnas.97.22.11990

[23]

10.1016/j.bbrc.2012.01.152

[24]

10.1111/j.1365-2958.2006.05097.x

[25]

THE UBIQUITIN SYSTEM

Avram Hershko, Aaron Ciechanover

Annual Review of Biochemistry 10.1146/annurev.biochem.67.1.425

[26]

10.1073/pnas.81.22.7021

[27]

10.1002/yea.2992

[28]

10.1371/journal.pone.0114590

[29]

10.1038/ncb2121

[30]

10.1073/pnas.0812316106

[31]

N-Terminal Acetylation of Cellular Proteins Creates Specific Degradation Signals

Cheol-Sang Hwang, Anna Shemorry, Alexander Varshavsky

Science 10.1126/science.1183147

[32]

10.1073/pnas.0808891105

[33]

A versatile toolbox for PCR‐based tagging of yeast genes: new fluorescent proteins, more markers and promoter substitution cassettes

Carsten Janke, Maria M. Magiera, Nicole Rathfelder et al.

Yeast 10.1002/yea.1142

[34]

10.1002/j.1460-2075.1992.tb05080.x

[35]

10.1074/jbc.270.29.17442

[36]

10.1016/j.bbrc.2004.06.105

[37]

10.1074/jbc.c400111200

[38]

10.1074/jbc.m513790200

[39]

10.1016/j.molcel.2018.03.033

[40]

10.1021/ac025747h

[41]

10.1038/nature14096

[42]

10.1038/nbt.2281

[43]

10.1007/978-1-4939-0944-5_13

[44]

10.1091/mbc.e15-07-0525

[45]

10.1091/mbc.e12-07-0548

[46]

10.1074/jbc.m112.401778

[47]

10.1002/(sici)1097-0061(199907)15:10b<963::aid-yea399>3.0.co;2-w

[48]

10.1016/s0092-8674(00)80574-7

[49]

10.1101/gad.1213904

[50]

Downregulation of N-terminal acetylation triggers ABA-mediated drought responses in Arabidopsis

Eric Linster, Iwona Stephan, Willy V. Bienvenut et al.

Nature Communications 10.1038/ncomms8640

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Published: Nov 11, 2021
Vol/Issue: 5(2)
Pages: e202000730
License: View

Authors

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Ilia Kats