scholarly journals The Hsp70/Hsp90 Co-Chaperone Hop/Stip1 Shifts the Proteostatic Balance from Folding Towards Degradation

2019 ◽  
Author(s):  
Kaushik Bhattacharya ◽  
Lorenz Weidenauer ◽  
Tania Morán Luengo ◽  
Pablo C. Echeverría ◽  
Lilia Bernasconi ◽  
...  

SUMMARYHop/Stip1/Sti1 is thought to be essential as a co-chaperone to facilitate substrate transfer between the Hsp70 and Hsp90 molecular chaperones. Despite this proposed key function for protein folding and maturation, it is not essential in a number of eukaryotes and bacteria lack an ortholog. We set out to identify and to characterize its eukaryote-specific function. Human cell lines and the budding yeast with deletions of the Hop/Sti1 gene display reduced proteasome activity due to inefficient capping of the core particle with regulatory particles. Unexpectedly, knock-out cells are more proficient at preventing protein aggregation and at promoting protein refolding. Without the restraint by Hop, a more efficient folding activity of the prokaryote-like Hsp70/Hsp90 complex, which can also be demonstrated in vitro, compensates for the proteasomal defect and ensures an alternate proteostatic equilibrium. Thus, cells may act on Hop to shift the proteostatic balance between folding and degradation.

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Kaushik Bhattacharya ◽  
Lorenz Weidenauer ◽  
Tania Morán Luengo ◽  
Ellis C. Pieters ◽  
Pablo C. Echeverría ◽  
...  

AbstractHop/Stip1/Sti1 is thought to be essential as a co-chaperone to facilitate substrate transfer between the Hsp70 and Hsp90 molecular chaperones. Despite this proposed key function for protein folding and maturation, it is not essential in a number of eukaryotes and bacteria lack an ortholog. We set out to identify and to characterize its eukaryote-specific function. Human cell lines and the budding yeast with deletions of the Hop/Sti1 gene display reduced proteasome activity due to inefficient capping of the core particle with regulatory particles. Unexpectedly, knock-out cells are more proficient at preventing protein aggregation and at promoting protein refolding. Without the restraint by Hop, a more efficient folding activity of the prokaryote-like Hsp70-Hsp90 complex, which can also be demonstrated in vitro, compensates for the proteasomal defect and ensures the proteostatic equilibrium. Thus, cells may act on the level and/or activity of Hop to shift the proteostatic balance between folding and degradation.


2021 ◽  
Vol 570 ◽  
pp. 206-213
Author(s):  
Ryohei Saito ◽  
Hiromasa Satoh ◽  
Kayo Aoba ◽  
Hajime Hirasawa ◽  
Naofumi Miwa

2005 ◽  
Vol 49 (4) ◽  
pp. 1597-1599 ◽  
Author(s):  
Benjamin Mimee ◽  
Caroline Labbé ◽  
René Pelletier ◽  
Richard R. Bélanger

ABSTRACT Flocculosin, a glycolipid isolated from the yeast-like fungus Pseudozyma flocculosa, was investigated for in vitro antifungal activity. The compound displayed antifungal properties against several pathogenic yeasts. Synergistic activity was observed between flocculosin and amphotericin B, and no significant cytotoxicity was demonstrated when tested against human cell lines.


1993 ◽  
Vol 13 (10) ◽  
pp. 6036-6043
Author(s):  
T Ogata ◽  
D Ayusawa ◽  
M Namba ◽  
E Takahashi ◽  
M Oshimura ◽  
...  

Using nontumorigenic immortalized human cell lines KMST-6 (KMST) and SUSM-1 (SUSM), we attempted to identify the chromosome that carries a putative senescence-related gene(s). These cell lines are the only ones that have been established independently from normal human diploid fibroblasts following in vitro mutagenesis. We first examined restriction fragment length polymorphisms on each chromosome of these immortalized cell lines and their parental cell lines and found specific chromosomal alterations common to these cell lines (a loss of heterozygosity in KMST and a deletion in SUSM) on the long arm of chromosome 7. In addition to these, we also found that introduction of chromosome 7 into these cell lines by means of microcell fusion resulted in the cessation of cell division, giving rise to cells resembling cells in senescence. Introduction of other chromosomes, such as chromosomes 1 and 11, on which losses of heterozygosity were also detected in one of the cell lines (KMST), to either KMST or SUSM cells or of chromosome 7 to several tumor-derived cell lines had no effect on their division potential. These results strongly suggest that a gene(s) affecting limited-division potential or senescence of normal human fibroblasts is located on chromosome 7, probably at the long arm of the chromosome, representing the first case in which a specific chromosome reverses the immortal phenotype of otherwise normal human cell lines.


2019 ◽  
Vol 17 (4) ◽  
pp. 497-506 ◽  
Author(s):  
Marta Henklewska ◽  
Aleksandra Pawlak ◽  
Justyna Kutkowska ◽  
Hanna Pruchnik ◽  
Andrzej Rapak ◽  
...  

2020 ◽  
Vol 47 (8) ◽  
pp. 3691-3702 ◽  
Author(s):  
Elisabeth Mara ◽  
Monika Clausen ◽  
Suphalak Khachonkham ◽  
Simon Deycmar ◽  
Clara Pessy ◽  
...  

1985 ◽  
Vol 133 (3) ◽  
pp. 548-548
Author(s):  
L.M. Wolf ◽  
K.E. Leitzel ◽  
H.A. Harvey ◽  
A. Lipton

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