Neuronal DnaJ proteins HSJ1a and HSJ1b: a role in linking the Hsp70 chaperone machine to the ubiquitin–proteasome system?

2004 ◽  
Vol 32 (4) ◽  
pp. 640-642 ◽  
Author(s):  
J.P. Chapple ◽  
J. van der Spuy ◽  
S. Poopalasundaram ◽  
M.E. Cheetham
Keyword(s):  
Protein Folding ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Ubiquitin Proteasome System ◽  
Cellular Protein ◽  
Hsp70 Chaperone ◽  
Ubiquitin Proteasome ◽  
Cellular Processing

The heat-shock protein 70 chaperone machine is functionally connected to the ubiquitin–proteasome system by the co-chaperone CHIP. In this article, we discuss evidence that the neuronal DnaJ proteins HSJ1a and HSJ1b may represent a further link between the cellular protein folding and degradation machineries. We have demonstrated that HSJ1 proteins contain putative ubiquitin interaction motifs and can modulate the cellular processing of rhodopsin, a protein that is targeted for degradation by the proteasome when it is misfolded.

Adenovirus E1A requires synthesis of a cellular protein to establish a stable transcription complex in injected Xenopus laevis oocytes

1987 ◽  
Vol 7 (9) ◽  
pp. 3049-3056
Author(s):  
J D Richter ◽  
H C Hurst ◽  
N C Jones
Keyword(s):  
Protein Synthesis ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Mammalian Cells ◽  
Cellular Protein ◽  
Xenopus Laevis Oocytes ◽  
Protein Synthesis Inhibitors ◽  
Adenovirus E1a ◽  
High Level

The Escherichia coli-expressed adenovirus E1A 13S mRNA product injected into Xenopus oocytes was active, as assessed by its ability to stimulate the transcription of an injected gene which is normally responsive to E1A in mammalian cells. In the presence of the protein synthesis inhibitors pactamycin or cycloheximide, E1A was correctly posttranslationally modified (phosphorylated) and transported to the nucleus; but it failed to stimulate the transcription of an injected gene containing the human heat shock protein 70 promoter. The basal (unstimulated) level of transcription of the gene was unaffected by these inhibitors. If oocytes were cultured in the presence of cycloheximide after E1A stimulated transcription, however, the high level of transcription was maintained for several hours without new protein synthesis. Results of competition studies with the same promoter (the heat shock protein 70 promoter) linked to two marked genes demonstrated that once the induction of transcription by E1A took place, the stimulated levels of transcription were maintained, even when they were challenged with excess competitor DNA. Results of these studies suggest that E1A requires the synthesis of a cellular protein to form a stable transcription complex.

scholarly journals Adenovirus E1A requires synthesis of a cellular protein to establish a stable transcription complex in injected Xenopus laevis oocytes.

1987 ◽  
Vol 7 (9) ◽  
pp. 3049-3056 ◽  
Author(s):  
J D Richter ◽  
H C Hurst ◽  
N C Jones
Keyword(s):  
Protein Synthesis ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Mammalian Cells ◽  
Cellular Protein ◽  
Xenopus Laevis Oocytes ◽  
Protein Synthesis Inhibitors ◽  
Adenovirus E1a ◽  
High Level

The Escherichia coli-expressed adenovirus E1A 13S mRNA product injected into Xenopus oocytes was active, as assessed by its ability to stimulate the transcription of an injected gene which is normally responsive to E1A in mammalian cells. In the presence of the protein synthesis inhibitors pactamycin or cycloheximide, E1A was correctly posttranslationally modified (phosphorylated) and transported to the nucleus; but it failed to stimulate the transcription of an injected gene containing the human heat shock protein 70 promoter. The basal (unstimulated) level of transcription of the gene was unaffected by these inhibitors. If oocytes were cultured in the presence of cycloheximide after E1A stimulated transcription, however, the high level of transcription was maintained for several hours without new protein synthesis. Results of competition studies with the same promoter (the heat shock protein 70 promoter) linked to two marked genes demonstrated that once the induction of transcription by E1A took place, the stimulated levels of transcription were maintained, even when they were challenged with excess competitor DNA. Results of these studies suggest that E1A requires the synthesis of a cellular protein to form a stable transcription complex.

Mechanism of substrate recognition by Hsp70 chaperones

2004 ◽  
Vol 32 (4) ◽  
pp. 617-621 ◽  
Author(s):  
A. Erbse ◽  
M.P. Mayer ◽  
B. Bukau
Keyword(s):  
Protein Folding ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Substrate Recognition ◽  
Short Peptide ◽  
Protein Substrates

The role of Hsp70 (heat-shock protein 70) chaperones in assisting protein-folding processes relies on their ability to associate with short peptide stretches of protein substrates in a transient and ATP-controlled manner. In the present study, we review the molecular details of the mechanism behind substrate recognition by Hsp70 proteins.

scholarly journals Heat Shock Protein 70 Regulates Degradation of the Mumps Virus Phosphoprotein via the Ubiquitin-Proteasome Pathway

2014 ◽  
Vol 89 (6) ◽  
pp. 3188-3199 ◽  
Author(s):  
Hiroshi Katoh ◽  
Toru Kubota ◽  
Shunsuke Kita ◽  
Yuichiro Nakatsu ◽  
Natsuko Aoki ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Cytoplasmic Inclusion ◽  
Mumps Virus ◽  
Viral Rna ◽  
Ubiquitin Proteasome Pathway ◽  
P Protein ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

ABSTRACTMumps virus (MuV) infection induces formation of cytoplasmic inclusion bodies (IBs). Growing evidence indicates that IBs are the sites where RNA viruses synthesize their viral RNA. However, in the case of MuV infection, little is known about the viral and cellular compositions and biological functions of the IBs. In this study, pulldown purification and N-terminal amino acid sequencing revealed that stress-inducible heat shock protein 70 (Hsp72) was a binding partner of MuV phosphoprotein (P protein), which was an essential component of the IB formation. Immunofluorescence and immunoblotting analyses revealed that Hsp72 was colocalized with the P protein in the IBs, and its expression was increased during MuV infection. Knockdown of Hsp72 using small interfering RNAs (siRNAs) had little, if any, effect on viral propagation in cultured cells. Knockdown of Hsp72 caused accumulation of ubiquitinated P protein and delayed P protein degradation. These results show that Hsp72 is recruited to IBs and regulates the degradation of MuV P protein through the ubiquitin-proteasome pathway.IMPORTANCEFormation of cytoplasmic inclusion bodies (IBs) is a common characteristic feature in mononegavirus infections. IBs are considered to be the sites of viral RNA replication and transcription. However, there have been few studies focused on host factors recruited to the IBs and their biological functions. Here, we identified stress-inducible heat shock protein 70 (Hsp72) as the first cellular partner of mumps virus (MuV) phosphoprotein (P protein), which is an essential component of the IBs and is involved in viral RNA replication/transcription. We found that the Hsp72 mobilized to the IBs promoted degradation of the MuV P protein through the ubiquitin-proteasome pathway. Our data provide new insight into the role played by IBs in mononegavirus infection.

scholarly journals Hsp90 Chaperones Bluetongue Virus Proteins and Prevents Proteasomal Degradation

2019 ◽  
Vol 93 (20) ◽  
Author(s):  
Bjorn-Patrick Mohl ◽  
Polly Roy
Keyword(s):  
Protein Folding ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Virus Replication ◽  
Heat Shock Protein 70 ◽  
Bluetongue Virus ◽  
Proteasomal Degradation ◽  
Viral Proteins ◽  
Protein Homeostasis ◽  
Virus Proteins

ABSTRACT The molecular chaperone machinery is important for the maintenance of protein homeostasis within the cells. The principle activities of the chaperone machinery are to facilitate protein folding and organize conformationally dynamic client proteins. Prominent among the members of the chaperone family are heat shock protein 70 (Hsp70) and 90 (Hsp90). Like cellular proteins, viral proteins depend upon molecular chaperones to mediate their stabilization and folding. Bluetongue virus (BTV), which is a model system for the Reoviridae family, is a nonenveloped arbovirus that causes hemorrhagic disease in ruminants. This constitutes a significant burden upon animals of commercial significance, such as sheep and cattle. Here, for the first time, we examined the role of chaperone proteins in the viral lifecycle of BTV. Using a combination of molecular, biochemical, and microscopic techniques, we examined the function of Hsp90 and its relevance to BTV replication. We demonstrate that Hsp70, the chaperone that is commonly usurped by viral proteins, does not influence virus replication, while Hsp90 activity is important for virus replication by stabilizing BTV proteins and preventing their degradation via the ubiquitin-proteasome pathway. To our knowledge this is the first report showing the involvement of Hsp90 as a modulator of BTV infection. IMPORTANCE Protein chaperones are instrumental for maintaining protein homeostasis, enabling correct protein folding and organization; prominent members include heat shock proteins 70 and 90. Virus infections place a large burden on this homeostasis. Identifying and understanding the underlying mechanisms that facilitate Bluetongue virus replication and spread through the usurpation of host factors is of primary importance for the development of intervention strategies. Our data identify and show that heat shock protein 90, but not heat shock protein 70, stabilizes bluetongue virus proteins, safeguarding them from proteasomal degradation.

scholarly journals Activation of Heat Shock Protein 70 as a Potential Therapeutic Strategy for the Treatment of Protein Folding Disease

2019 ◽  
Vol 33 (S1) ◽  
Author(s):  
Amanda Davis ◽  
Haoming Zhang ◽  
Miranda Lau ◽  
Sumita Chakraborty ◽  
Yoshihiro Morishima ◽  
...  
Keyword(s):  
Protein Folding ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Therapeutic Strategy

scholarly journals Cochaperones enable Hsp70 to fold proteins like a Maxwell’s demon

2018 ◽  
Author(s):  
Huafeng Xu
Keyword(s):  
Free Energy ◽  
Protein Folding ◽  
Heat Shock ◽  
Heat Shock Protein 70 ◽  
Protein Quality ◽  
Atp Hydrolysis ◽  
Cellular Protein ◽  
Native State ◽  
Refolding Kinetics ◽  
Stimulation Of

AbstractThe heat shock protein 70 (Hsp70) chaperones, vital to the proper folding of proteins inside cells, consume ATP and require cochaperones in assisting protein folding. It is unclear whether Hsp70 can utilize the free energy from ATP hydrolysis to fold a protein into a native state that is thermodynamically unstable in the chaperone-free equilibrium. Here we present a model of Hsp70-mediated protein folding, which predicts that Hsp70, as a result of differential stimulation of ATP hydrolysis by its Hsp40 cochaperone, dissociates faster from a substrate in fold-competent conformations than from one in misfolding-prone conformations, thus elevating the native concentration above and suppressing the misfolded concentration below their respective equilibrium values. Previous models would not make or imply these predictions, which are experimentally testable. Our model quantitatively reproduces experimental refolding kinetics, predicts how modulations of the Hsp70/Hsp40 chaperone system affect protein folding, and suggests new approaches to regulating cellular protein quality.

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