scholarly journals Inhibiting heat shock protein 90 and the ubiquitin‐proteasome pathway impairs metabolic homeostasis and leads to cell death in human pancreatic cancer cells

Cancer ◽  
2017 ◽  
Vol 123 (24) ◽  
pp. 4924-4933 ◽  
Author(s):  
Astrid Belalcazar ◽  
Walid L. Shaib ◽  
Matthew R. Farren ◽  
Chao Zhang ◽  
Zhengjia Chen ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Death ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90 ◽  
Human Pancreatic Cancer ◽  
Ubiquitin Proteasome Pathway ◽  
Pancreatic Cancer Cells ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

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 Withaferin A targets heat shock protein 90 in pancreatic cancer cells

2010 ◽  
Vol 79 (4) ◽  
pp. 542-551 ◽  
Author(s):  
Yanke Yu ◽  
Adel Hamza ◽  
Tao Zhang ◽  
Mancang Gu ◽  
Peng Zou ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Cancer Cells ◽  
Heat Shock Protein 90 ◽  
Withaferin A ◽  
Pancreatic Cancer Cells

scholarly journals The Degradation of Apolipoprotein B100 Is Mediated by the Ubiquitin-proteasome Pathway and Involves Heat Shock Protein 70

1997 ◽  
Vol 272 (33) ◽  
pp. 20427-20434 ◽  
Author(s):  
Edward A. Fisher ◽  
Mingyue Zhou ◽  
Deborah M. Mitchell ◽  
Xujun Wu ◽  
Satoshi Omura ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 70 ◽  
Ubiquitin Proteasome Pathway ◽  
Apolipoprotein B100 ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

scholarly journals Enzyme-treated Asparagus Extract Down-regulates Heat Shock Protein 27 of Pancreatic Cancer Cells

In Vivo ◽  
2018 ◽  
Vol 32 (4) ◽  
pp. 759-763 ◽  
Author(s):  
TAKUYA SHIMADA ◽  
YUTA NANIMOTO ◽  
BYRON BARON ◽  
TAKAO KITAGAWA ◽  
KAZUHIRO TOKUDA ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Cancer Cells ◽  
Heat Shock Protein 27 ◽  
Pancreatic Cancer Cells

Abstract 44: TAK1 Regulates Caspase 8 Activation and Necroptotic Signaling via Multiple Cell Death Checkpoints

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Xaioyun Guo ◽  
Haifeng Yin ◽  
Yi Chen ◽  
Lei Li ◽  
Jing Li ◽  
...  
Keyword(s):  
Cell Death ◽  
Adaptor Protein ◽  
Regulatory Mechanisms ◽  
Caspase 8 ◽  
Ubiquitin Proteasome Pathway ◽  
Pathological Conditions ◽  
Ubiquitin Proteasome ◽  
Multiple Cell ◽  
Proteasome Pathway

Necroptosis has emerged as a new form of programmed cell death implicated in a number of pathological conditions such as ischemic injury, neurodegenerative disease, and viral infection. Recent studies indicate that TGFβ-activated kinase 1 (TAK1) is nodal regulator of necroptotic cell death, but the underlying molecular regulatory mechanisms remain elusive. Here we reported that TAK1 regulates necroptotic signaling as well as caspase 8 activation through both NFκB-dependent and -independent mechanisms. Inhibition of TAK1 promoted TNFα-induced necroptosis through the induction of RIP1 phosphorylation/activation and necrosome formation, in the presence of ongoing caspase activation. Further, inhibition of TAK1 triggered two caspase 8 activation pathways through the induction of RIP1-FADD-caspase 8 complex as well as FLIP cleavage/degradation. Mechanistically, our data uncovered an essential role of the adaptor protein TRADD in caspase 8 activation and necrosome formation triggered by TAK1 inhibition. Moreover, ablation of the deubiqutinase CYLD prevented both apoptotic and necroptotic signaling induced by TAK1 inhibition, whereas deletion of the E3 ubiquitin ligase TRAF2 had the opposite effect. Finally, blocking the ubiquitin-proteasome pathway prevented the degradation of key necroptotic signaling proteins and necrosome formation. Thus we identified novel regulatory mechanisms underling the critical role of TAK1 in necroptotic signaling through regulation of multiple cell death checkpoints. Targeting key components of the necroptotic pathway (e.g., TRADD and CYLD) and the ubiquitin-proteasome pathway may represent novel therapeutic strategies for pathological conditions driven by necroptosis.

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