Control of Hsp90 chaperone and its clients by N-terminal acetylation and the N-end rule pathway

Proceedings of the National Academy of Sciences of the United States of America
Jang-Hyun OhA Varshavsky

Abstract

We found that the heat shock protein 90 (Hsp90) chaperone system of the yeast Saccharomyces cerevisiae is greatly impaired in naa10Δ cells, which lack the NatA Nα-terminal acetylase (Nt-acetylase) and therefore cannot N-terminally acetylate a majority of normally N-terminally acetylated proteins, including Hsp90 and most of its cochaperones. Chk1, a mitotic checkpoint kinase and a client of Hsp90, was degraded relatively slowly in wild-type cells but was rapidly destroyed in naa10Δ cells by the Arg/N-end rule pathway, which recognized a C terminus-proximal degron of Chk1. Diverse proteins (in addition to Chk1) that are shown here to be targeted for degradation by the Arg/N-end rule pathway in naa10Δ cells include Kar4, Tup1, Gpd1, Ste11, and also, remarkably, the main Hsp90 chaperone (Hsc82) itself. Protection of Chk1 by Hsp90 could be overridden not only by ablation of the NatA Nt-acetylase but also by overexpression of the Arg/N-end rule pathway in wild-type cells. Split ubiquitin-binding assays detected interactions between Hsp90 and Chk1 in wild-type cells but not in naa10Δ cells. These and related results revealed a major role of Nt-acetylation in the Hsp90-mediated protein homeostasis, a strong up-regulation of the Arg/N-...Continue Reading

References

Mar 24, 1989·Cell·A Bachmair, A Varshavsky
Oct 25, 1994·Proceedings of the National Academy of Sciences of the United States of America·N Johnsson, A Varshavsky
Jul 6, 2002·Science·Yong Tae KwonAlexander Varshavsky
Feb 20, 2007·Trends in Cell Biology·Axel MogkBernd Bukau
Nov 27, 2008·Proceedings of the National Academy of Sciences of the United States of America·Cheol-Sang Hwang, Alexander Varshavsky
Apr 30, 2009·Cell Division·Claudia Tapia-AlvealMatthew J O'Connell
Jul 14, 2009·Nucleic Acids Research·Peter KötterBeatrix Suess
Oct 21, 2009·Nature Chemical Biology·Erin K SchraderAndreas Matouschek
Jan 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jarrod W HeckRandolph Y Hampton
Jan 30, 2010·Science·Cheol-Sang HwangAlexander Varshavsky
May 14, 2010·Molecular Biology of the Cell·Nadinath B NillegodaAvrom J Caplan
Jun 10, 2010·Nature Reviews. Molecular Cell Biology·Mikko TaipaleSusan Lindquist
Sep 14, 2010·Nature Structural & Molecular Biology·Woo Suk ChoiHyun Kyu Song
Nov 16, 2010·Nature Cell Biology·Cheol-Sang HwangAlexander Varshavsky
Jun 3, 2011·Protein Science : a Publication of the Protein Society·Alexander Varshavsky
Jul 22, 2011·Nature·F Ulrich HartlManajit Hayer-Hartl
Jul 26, 2011·Biochimica Et Biophysica Acta·D A DouganK N Truscott
Aug 16, 2011·Biochimica Et Biophysica Acta·Chrisostomos Prodromou
Sep 23, 2011·Methods in Molecular Biology·Alexander DünklerNils Johnsson
Apr 25, 2012·Annual Review of Biochemistry·Takafumi TasakiYong Tae Kwon
Jun 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Konstantin I PiatkovAlexander Varshavsky
Jul 31, 2012·Biochemical and Biophysical Research Communications·Rupali PrasadDavis T W Ng
Sep 15, 2012·Nature Reviews. Microbiology·Michelle D LeachAlistair J P Brown
Mar 7, 2013·Nature Reviews. Molecular Cell Biology·Evan T Powers, William E Balch
Mar 19, 2013·Molecular Cell·Christopher S BrowerAlexander Varshavsky
Apr 16, 2013·Molecular Cell·Stefanie DuttlerJudith Frydman
Jun 29, 2013·Biomedical Journal·Jing Li, Johannes Buchner
Oct 15, 2013·Autophagy·Koji Yamano, Richard J Youle
Dec 24, 2013·Cell·Heon-Ki KimCheol-Sang Hwang
Apr 1, 2014·Cell·Suzanne WolffAndrew Dillin
May 31, 2014·Trends in Cell Biology·Daniel J GibbsMichael J Holdsworth
Jul 16, 2014·Nature Communications·William M HolmesTricia R Serio
Jan 13, 2015·Trends in Biochemical Sciences·G Elif Karagöz, Stefan G D Rüdiger

❮ Previous
Next ❯

Citations

Dec 19, 2017·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Mohamed A EldeebRichard P Fahlman
Jul 29, 2018·Experimental & Molecular Medicine·Kha The NguyenCheol-Sang Hwang
Nov 11, 2017·The Journal of Biological Chemistry·Jang-Hyun OhAlexander Varshavsky
Mar 11, 2020·Microbial Biotechnology·Antoine DanchinConghui You
Jul 29, 2018·Experimental & Molecular Medicine·Rasmus ReeThomas Arnesen
Jul 25, 2019·Proceedings of the National Academy of Sciences of the United States of America·Artem MelnykovAlexander Varshavsky
Nov 10, 2018·Science·Jeong-Mok KimCheol-Sang Hwang
Jan 10, 2019·Proceedings of the National Academy of Sciences of the United States of America·Alexander Varshavsky
Jun 10, 2020·Proceedings of the National Academy of Sciences of the United States of America·Cheng DongJinrong Min
Jul 29, 2018·Experimental & Molecular Medicine·Katherine J KuhnsWanguo Liu
May 6, 2020·Proceedings of the National Academy of Sciences of the United States of America·Jang-Hyun OhAlexander Varshavsky
Nov 25, 2020·Proceedings of the National Academy of Sciences of the United States of America·Tri T M VuAlexander Varshavsky
Aug 10, 2019·Biochemical and Biophysical Research Communications·Ifeoluwapo Matthew Joshua, Thomas Höfken
Jan 3, 2020·Biochemistry·Shun-Jia ChenAlexander Varshavsky
Jan 29, 2020·Neurobiology of Disease·Rodrigo Vinueza-GavilanesMontserrat Arrasate
Jul 22, 2020·Biochemistry·Tri T M Vu, Alexander Varshavsky
Oct 8, 2020·ACS Synthetic Biology·Andrew S Gaynor, Wilfred Chen

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.