scholarly journals Heat-Shock Protein 90 Controls the Expression of Cell-Cycle Genes by Stabilizing Metazoan-Specific Host-Cell Factor HCFC1

Cell Reports ◽  
2019 ◽  
Vol 29 (6) ◽  
pp. 1645-1659.e9 ◽  
Author(s):  
Aneliya Antonova ◽  
Barbara Hummel ◽  
Ashkan Khavaran ◽  
Desiree M. Redhaber ◽  
Fernando Aprile-Garcia ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Host Cell ◽  
Heat Shock Protein 90 ◽  
Cell Cycle Genes ◽  
Specific Host ◽  
Host Cell Factor

scholarly journals Geldanamycin, a Ligand of Heat Shock Protein 90, Inhibits the Replication of Herpes Simplex Virus Type 1 In Vitro

2004 ◽  
Vol 48 (3) ◽  
pp. 867-872 ◽  
Author(s):  
Yu-Huan Li ◽  
Pei-Zhen Tao ◽  
Yu-Zhen Liu ◽  
Jian-Dong Jiang
Keyword(s):  
Cell Cycle ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90 ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Geldanamycin (GA) is an antibiotic targeting the ADP/ATP binding site of heat shock protein 90 (Hsp90). In screening for anti-herpes simplex virus type 1 (HSV-1) candidates, we found GA active against HSV-1. HSV-1 replication in vitro was significantly inhibited by GA with an 50% inhibitory concentration of 0.093 μM and a concentration that inhibited cellular growth 50% in comparison with the results seen with untreated controls of 350 μM. The therapeutic index of GA was over 3,700 (comparable to the results seen with acyclovir). GA did not inhibit HSV-1 thymidine kinase. Cells infected with HSV-1 demonstrated cell cycle arrest at the G1/S transition; however, treatment with GA resulted in a cell cycle distribution pattern identical to that of untreated cells, indicating a restoration of cell growth in HSV-1-infected cells by GA treatment. Accordingly, HSV-1 DNA synthesis was suppressed in HSV-1+ cells treated with GA. The antiviral mechanism of GA appears to be associated with Hsp90 inactivation and cell cycle restoration, which indicates that GA exhibits broad-spectrum antiviral activity. Indeed, GA exhibited activities in vitro against other viruses, including severe acute respiratory syndrome coronavirus. Since GA inhibits HSV-1 through a cellular mechanism unique among HSV-1 agents, we consider it a new candidate agent for HSV-1.

Heat Shock Protein 90 (HSP90) Is Overexpressed in Primary and Cultured Hodgkin Lymphoma (HL) Cells: Role of Therapeutic Targeting Using the Small Molecule Inhibitor 17-AAG.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2422-2422
Author(s):  
Georgios V. Georgakis ◽  
Yang Li ◽  
George Z. Rassidakis ◽  
L. Jeffrey Medeiros ◽  
Anas Younes
Keyword(s):  
Cell Cycle ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Cell Cycle Arrest ◽  
Hodgkin Lymphoma ◽  
Small Molecule ◽  
Heat Shock Protein 90 ◽  
Conventional Chemotherapy ◽  
Cycle Arrest ◽  
Molecule Inhibitor

Abstract Conventional chemotherapy is the golden standard for therapy of Hodgkin Lymphoma (HL). Nevertheless, considerable toxicity and secondary malignancies indicate the need for targeted therapy that preferentially kills the malignant cells. The molecular chaperone heat shock protein 90 (HSP90) is expressed in all mammalian cells, but it is overexpressed in malignancy. 17-AAG, a small molecule inhibitor of HSP90, has been shown to induce apoptosis and cell cycle arrest in a variety of tumor types. In the present study we show that HSP90 is overexpressed in the primary Hodgkin and Reed-Sternberg (HRS) cells, as well as in HL derived cells lines. Inhibition of HSP90 17-AAG showed antiproliferative effect in HL derived cell lines in a dose dependent manner. Cell death was due to apoptosis, as determined by Annexin-V staining and FACS analysis. Apoptosis was mediated by the activation of the caspase pathway, especially by caspase 8, 9, and 3. Inhibition of caspase activity by the pancaspase inhibitor Z-VAD-FMK partially reversed the 17-AAG lethal effect. 17-AAG had no significant on the level of the antiapoptotic Bcl-2 family members or the cellular or X-Linked inhibitors of apoptosis. In contrast, there was considerable degradation of cFLIP. Moreover, 17-AAG treatment reduced the intracellular levels of molecules that have been shown to be of key importance in HRS cell survival and proliferation, including AKT and the phosphorylated ERK1/2, but with minimal change in total ERK1/2. Cell cycle arrest was observed at G0/G1 or at G2/M phase, and was mediated by reduction in the levels of MDM2, cyclin D1 with cdk4 and cdk6, and cyclin B1. The potential synergy of 17-AAG with conventional chemotherapy and anti-TRAIL death receptor monoclonal antibody, was explored by the simultaneous incubation of HL derived cells with both doxorubicin or antibodies against TRAIL receptors R1 and R2, respectively. The combination of 17-AAG with doxorubicin or anti-TRAIL antibodies was significantly more effective than either agent alone. Based on these data we are conducting a phase II study of 17-AAG in patients with relapsed classical HL.

scholarly journals Heat Shock Protein 90-Independent Activation of Truncated Hepadnavirus Reverse Transcriptase

2003 ◽  
Vol 77 (8) ◽  
pp. 4471-4480 ◽  
Author(s):  
Xingtai Wang ◽  
Xiaofeng Qian ◽  
Hwai-Chen Guo ◽  
Jianming Hu
Keyword(s):  
Heat Shock ◽  
Hepatitis B ◽  
Heat Shock Protein ◽  
Reverse Transcriptase ◽  
Host Cell ◽  
Specific Interaction ◽  
Heat Shock Protein 90 ◽  
Cytoplasmic Factor ◽  
Duck Hepatitis ◽  
Protein Priming

ABSTRACT The reverse transcriptase (RT) encoded by hepadnaviruses (hepatitis B viruses) is a multifunctional protein critical for several aspects of viral assembly and replication. Reverse transcription is triggered by the specific interaction between the RT and an RNA signal located on the viral pregenomic RNA, termed ε, and is initiated through a novel protein priming mechanism whereby the RT itself serves as a protein primer and ε serves as the obligatory template. Using the RT from duck hepatitis B virus as a model, we previously demonstrated that RT-ε interaction and protein priming require the assistance of a host cell chaperone complex, heat shock protein 90 (Hsp90) and its cochaperones, which associates with the RT and facilitates the folding of the RT into an active conformation. We now report that extensive truncation removing the entire C-terminal RNase H domain and part of the central RT domain could relieve this dependence on Hsp90 for RT folding such that the truncated RT variants could function in ε interaction and protein priming independently of Hsp90. The presence of certain nonionic or zwitterionic detergent was sufficient to establish and maintain the truncated RT proteins in an active, albeit labile, state. Furthermore, we were able to refold an RT truncation variant de novo after complete denaturation. In contrast, the full-length RT and also RT variants with less-extensive C-terminal truncations required Hsp90 for activation. Surprisingly, the presence of detergent plus some yet-to-be-identified cytoplasmic factor(s) led to a dramatic suppression of the RT activities. These results have important implications for RT folding and conformational maturation, Hsp90 chaperone function, and potential inhibition of RT functions by host cell factors.

Glycyrrhizin effects rat hepatocytes via the reduction of heat shock protein 90 expression

2001 ◽  
Vol 120 (5) ◽  
pp. A357-A357
Author(s):  
T YOH ◽  
T NAKASHIMA ◽  
Y SUMIDA ◽  
Y KAKISAKA ◽  
H ISHIKAWA ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90 ◽  
Rat Hepatocytes
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