Compartment-specific aggregases direct distinct nuclear and cytoplasmic aggregate deposition
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Compartment-specific aggregases direct distinct nuclear and cytoplasmic aggregate deposition. / Miller, Stephanie Bm; Ho, Chi-Ting; Winkler, Juliane; Khokhrina, Maria; Neuner, Annett; Mohamed, Mohamed Yh; Guilbride, D Lys; Richter, Karsten; Lisby, Michael; Schiebel, Elmar; Mogk, Axel; Bukau, Bernd.
I: E M B O Journal, Bind 34, Nr. 6, 2015, s. 778-797.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Compartment-specific aggregases direct distinct nuclear and cytoplasmic aggregate deposition
AU - Miller, Stephanie Bm
AU - Ho, Chi-Ting
AU - Winkler, Juliane
AU - Khokhrina, Maria
AU - Neuner, Annett
AU - Mohamed, Mohamed Yh
AU - Guilbride, D Lys
AU - Richter, Karsten
AU - Lisby, Michael
AU - Schiebel, Elmar
AU - Mogk, Axel
AU - Bukau, Bernd
N1 - © 2015 The Authors.
PY - 2015
Y1 - 2015
N2 - Disruption of the functional protein balance in living cells activates protective quality control systems to repair damaged proteins or sequester potentially cytotoxic misfolded proteins into aggregates. The established model based on Saccharomyces cerevisiae indicates that aggregating proteins in the cytosol of eukaryotic cells partition between cytosolic juxtanuclear (JUNQ) and peripheral deposits. Substrate ubiquitination acts as the sorting principle determining JUNQ deposition and subsequent degradation. Here, we show that JUNQ unexpectedly resides inside the nucleus, defining a new intranuclear quality control compartment, INQ, for the deposition of both nuclear and cytosolic misfolded proteins, irrespective of ubiquitination. Deposition of misfolded cytosolic proteins at INQ involves chaperone-assisted nuclear import via nuclear pores. The compartment-specific aggregases, Btn2 (nuclear) and Hsp42 (cytosolic), direct protein deposition to nuclear INQ and cytosolic (CytoQ) sites, respectively. Intriguingly, Btn2 is transiently induced by both protein folding stress and DNA replication stress, with DNA surveillance proteins accumulating at INQ. Our data therefore reveal a bipartite, inter-compartmental protein quality control system linked to DNA surveillance via INQ and Btn2.
AB - Disruption of the functional protein balance in living cells activates protective quality control systems to repair damaged proteins or sequester potentially cytotoxic misfolded proteins into aggregates. The established model based on Saccharomyces cerevisiae indicates that aggregating proteins in the cytosol of eukaryotic cells partition between cytosolic juxtanuclear (JUNQ) and peripheral deposits. Substrate ubiquitination acts as the sorting principle determining JUNQ deposition and subsequent degradation. Here, we show that JUNQ unexpectedly resides inside the nucleus, defining a new intranuclear quality control compartment, INQ, for the deposition of both nuclear and cytosolic misfolded proteins, irrespective of ubiquitination. Deposition of misfolded cytosolic proteins at INQ involves chaperone-assisted nuclear import via nuclear pores. The compartment-specific aggregases, Btn2 (nuclear) and Hsp42 (cytosolic), direct protein deposition to nuclear INQ and cytosolic (CytoQ) sites, respectively. Intriguingly, Btn2 is transiently induced by both protein folding stress and DNA replication stress, with DNA surveillance proteins accumulating at INQ. Our data therefore reveal a bipartite, inter-compartmental protein quality control system linked to DNA surveillance via INQ and Btn2.
U2 - 10.15252/embj.201489524
DO - 10.15252/embj.201489524
M3 - Journal article
C2 - 25672362
VL - 34
SP - 778
EP - 797
JO - E M B O Journal
JF - E M B O Journal
SN - 0261-4189
IS - 6
ER -
ID: 136305738