Rapamycin promotes autophagy cell death of Kaposi’s sarcoma cells through P75NTR activation

2021 ◽  
Author(s):  
Simona Lupinacci ◽  
Anna Perri ◽  
Giuseppina Toteda ◽  
Donatella Vizza ◽  
Danilo Lofaro ◽  
...  
Keyword(s):  
Cell Death ◽  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Sarcoma Cells

Identification of a major growth factor for AIDS-Kaposi's sarcoma cells as oncostatin M

Science ◽  
1992 ◽  
Vol 255 (5050) ◽  
pp. 1430-1432 ◽  
Author(s):  
B. Nair ◽  
A. DeVico ◽  
S Nakamura ◽  
T. Copeland ◽  
Y Chen ◽  
...  
Keyword(s):  
Growth Factor ◽  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Oncostatin M ◽  
Sarcoma Cells

Phenotypic alterations in Kaposi’s sarcoma cells by antisense reduction of perlecan

2000 ◽  
Vol 6 (1) ◽  
pp. 10-17 ◽  
Author(s):  
Chiara Marchisone ◽  
Federica Del Grosso ◽  
Luciana Masiello ◽  
Maria Prat ◽  
Leonardo Santi ◽  
...  
Keyword(s):  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Sarcoma Cells

scholarly journals Role of Pax2 in Apoptosis Resistance and Proinvasive Phenotype of Kaposi's Sarcoma Cells

2003 ◽  
Vol 279 (6) ◽  
pp. 4136-4143 ◽  
Author(s):  
Stefano Buttiglieri ◽  
Maria Chiara Deregibus ◽  
Stefania Bravo ◽  
Paola Cassoni ◽  
Roberto Chiarle ◽  
...  
Keyword(s):  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Apoptosis Resistance ◽  
Sarcoma Cells

Antiproliferative Properties of Toremifene on AIDS-Related Kaposi’s Sarcoma Cells

Chemotherapy ◽  
2002 ◽  
Vol 48 (5) ◽  
pp. 238-243 ◽  
Author(s):  
Angela Hong ◽  
Bryan R. Leigh
Keyword(s):  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Sarcoma Cells

Expression of functional tyrosine kinases on immortalized Kaposi's sarcoma cells

2000 ◽  
Vol 184 (2) ◽  
pp. 246-254 ◽  
Author(s):  
Fabrizio Montaldo ◽  
Antonella Maff� ◽  
Monica Morini ◽  
Douglas Noonan ◽  
Silvia Giordano ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Kaposi's Sarcoma ◽  
Kaposi’S Sarcoma ◽  
Sarcoma Cells

scholarly journals HACE1, an E3 Ubiquitin Protein Ligase, Mitigates Kaposi’s Sarcoma-Associated Herpesvirus Infection-Induced Oxidative Stress by Promoting Nrf2 Activity

2019 ◽  
Vol 93 (9) ◽  
Author(s):  
Binod Kumar ◽  
Arunava Roy ◽  
Kumari Asha ◽  
Neelam Sharma-Walia ◽  
Mairaj Ahmed Ansari ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Kaposi's Sarcoma ◽  
Nuclear Translocation ◽  
Kaposi’S Sarcoma ◽  
Induce Cell Death ◽  
Kshv Infection ◽  
Ubiquitin Protein Ligase ◽  
Viral Genes ◽  
Infected Cells

ABSTRACTKaposi’s sarcoma-associated herpesvirus (KSHV)-induced activation of nuclear factor erythroid 2-related factor 2 (Nrf2) is essential for both the expression of viral genes (latency) and modulation of the host antioxidant machinery. Reactive oxygen species (ROS) are also regulated by the ubiquitously expressed HACE1 protein (HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1), which targets the Rac1 protein for proteasomal degradation, and this blocks the generation of ROS by Rac1-dependent NADPH oxidases. In this study, we examined the role of HACE1 in KSHV infection. Elevated levels of HACE1 expression were observed inde novoKSHV-infected endothelial cells, KSHV latently infected TIVE-LTC and PEL cells, and Kaposi’s sarcoma skin lesion cells. The increased HACE1 expression in the infected cells was mediated by KSHV latent protein kaposin A. HACE1 knockdown resulted in high Rac1 and Nox 1 (NADPH oxidase 1) activity, increased ROS (oxidative stress), increased cell death, and decreased KSHV gene expression. Loss of HACE1 impaired KSHV infection-induced phosphoinositide 3-kinase (PI3-K), protein kinase C-ζ (PKC-ζ), extracellular signal-regulated kinase 1/2 (ERK1/2), NF-κB, and Nrf2 activation and nuclear translocation of Nrf2, and it reduced the expression of Nrf2 target genes responsible for balancing the oxidative stress. In the absence of HACE1, glutamine uptake increased in the cells to cope with the KSHV-induced oxidative stress. These findings reveal for the first time that HACE1 plays roles during viral infection-induced oxidative stress and demonstrate that HACE1 facilitates resistance to KSHV infection-induced oxidative stress by promoting Nrf2 activity. Our studies suggest that HACE1 could be a potential target to induce cell death in KSHV-infected cells and to manage KSHV infections.IMPORTANCEROS play important roles in several cellular processes, and increased ROS cause several adverse effects. KSHV infection of endothelial cells induces ROS, which facilitate virus entry by amplifying the infection-induced host cell signaling cascade, which, in turn, induces the nuclear translocation of phospho-Nrf2 protein to regulate the expression of antioxidative genes and viral genes. The present study demonstrates that KSHV infection induces the E3 ligase HACE1 protein to regulate KSHV-induced oxidative stress by promoting the activation of Nrf2 and nuclear translocation. Absence of HACE1 results in increased ROS and cellular death and reduced nuclear Nrf2, antioxidant, and viral gene expression. Together, these studies suggest that HACE1 can be a potential target to induce cell death in KSHV-infected cells.

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