Most misfolded cytosolic proteins in the cell are eliminated by the
ubiquitin-proteasome system. In yeast, polyubiquitination of misfolded
cytosolic proteins is triggered mainly by the action of two ubiquitin
ligases Ubr1, formerly discovered as recognition component of the N-end
rule pathway, and the nuclear ubiquitin ligase San1. For San1-mediated
targeting to proteasomal degradation, cytosolic proteins have to be
imported into the nucleus. Selection of misfolded substrates for import
into the nucleus had remained elusive. This study shows that an
increasing molecular mass of substrates prevents nuclear San1-triggered
proteasomal degradation but renders them susceptible to cytoplasmic
Ubr1-triggered degradation.
We thank Davis Ng for providing the plasmid pSK146. We also thank
Christiana Lungu for assistance with the indirect immunofluorescence
experiments. This work has been supported by the Deutsche
Forschungsgemeinschaft, Bonn.
%0 Journal Article
%1 ISI:000379153500011
%A Amm, Ingo
%A Wolf, Dieter H.
%C 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
%D 2016
%I WILEY-BLACKWELL
%J FEBS LETTERS
%K San1; Ubr1} control; cytosolic ligase; nucleus; protein proteins; quality ubiquitin {Misfolded
%N 12
%P 1765-1775
%R 10.1002/1873-3468.12213
%T Molecular mass as a determinant for nuclear San1-dependent targeting of
misfolded cytosolic proteins to proteasomal degradation
%V 590
%X Most misfolded cytosolic proteins in the cell are eliminated by the
ubiquitin-proteasome system. In yeast, polyubiquitination of misfolded
cytosolic proteins is triggered mainly by the action of two ubiquitin
ligases Ubr1, formerly discovered as recognition component of the N-end
rule pathway, and the nuclear ubiquitin ligase San1. For San1-mediated
targeting to proteasomal degradation, cytosolic proteins have to be
imported into the nucleus. Selection of misfolded substrates for import
into the nucleus had remained elusive. This study shows that an
increasing molecular mass of substrates prevents nuclear San1-triggered
proteasomal degradation but renders them susceptible to cytoplasmic
Ubr1-triggered degradation.
@article{ISI:000379153500011,
abstract = {{Most misfolded cytosolic proteins in the cell are eliminated by the
ubiquitin-proteasome system. In yeast, polyubiquitination of misfolded
cytosolic proteins is triggered mainly by the action of two ubiquitin
ligases Ubr1, formerly discovered as recognition component of the N-end
rule pathway, and the nuclear ubiquitin ligase San1. For San1-mediated
targeting to proteasomal degradation, cytosolic proteins have to be
imported into the nucleus. Selection of misfolded substrates for import
into the nucleus had remained elusive. This study shows that an
increasing molecular mass of substrates prevents nuclear San1-triggered
proteasomal degradation but renders them susceptible to cytoplasmic
Ubr1-triggered degradation.}},
added-at = {2017-05-18T11:32:12.000+0200},
address = {{111 RIVER ST, HOBOKEN 07030-5774, NJ USA}},
affiliation = {{Wolf, DH (Reprint Author), Univ Stuttgart, Inst Biochem, Pfaffenwaldring 55, D-70569 Stuttgart, Germany.
Amm, Ingo; Wolf, Dieter H., Univ Stuttgart, Inst Biochem, Pfaffenwaldring 55, D-70569 Stuttgart, Germany.}},
author = {Amm, Ingo and Wolf, Dieter H.},
author-email = {{dieter.wolf@ibc.uni-stuttgart.de}},
biburl = {https://puma.ub.uni-stuttgart.de/bibtex/2994f989a00fe4666b71936da55f5d2db/hermann},
doi = {{10.1002/1873-3468.12213}},
eissn = {{1873-3468}},
funding-acknowledgement = {{Deutsche Forschungsgemeinschaft, Bonn}},
funding-text = {{We thank Davis Ng for providing the plasmid pSK146. We also thank
Christiana Lungu for assistance with the indirect immunofluorescence
experiments. This work has been supported by the Deutsche
Forschungsgemeinschaft, Bonn.}},
interhash = {a5c5122cf5385964b38e7ccc5f219851},
intrahash = {994f989a00fe4666b71936da55f5d2db},
issn = {{0014-5793}},
journal = {{FEBS LETTERS}},
keywords = {San1; Ubr1} control; cytosolic ligase; nucleus; protein proteins; quality ubiquitin {Misfolded},
keywords-plus = {{QUALITY-CONTROL DEGRADATION; ER-ASSOCIATED DEGRADATION; END RULE
PATHWAY; UBIQUITIN LIGASE; EXPOSED HYDROPHOBICITY; YEAST; SYSTEM; UBR1;
RECOGNITION; SUBSTRATE}},
language = {{English}},
month = {{JUN}},
number = {{12}},
number-of-cited-references = {{39}},
pages = {{1765-1775}},
publisher = {{WILEY-BLACKWELL}},
research-areas = {{Biochemistry \& Molecular Biology; Biophysics; Cell Biology}},
times-cited = {{1}},
timestamp = {2017-05-18T09:32:12.000+0200},
title = {{Molecular mass as a determinant for nuclear San1-dependent targeting of
misfolded cytosolic proteins to proteasomal degradation}},
type = {{Article}},
volume = {{590}},
web-of-science-categories = {{Biochemistry \& Molecular Biology; Biophysics; Cell Biology}},
year = {{2016}}
}