The human herpesvirus 8 (HHV8, also called Kaposi's sarcoma-associated herpesvirus) has been linked to Kaposi's sarcoma and primary effusion lymphoma (PEL) in immunocompromised individuals. We demonstrate that PEL cell lines have a constitutively active NF-kappaB pathway, which is associated with persistent phosphorylation of IkappaBalpha. To elucidate the mechanism of NF-kappaB activation in PEL cell lines, we have investigated the role of viral FLICE inhibitory protein (vFLIP) in this process. We report that stable expression of HHV8 vFLIP in a variety of cell lines is associated with persistent NF-kappaB activation caused by constitutive phosphorylation of IkappaBalpha. HHV8 vFLIP gets recruited to a approximately 700-kDa IkappaB kinase (IKK) complex and physically associates with IKKalpha, IKKbeta, NEMO/IKKgamma, and RIP. HHV8 vFLIP is incapable of activating NF-kappaB in cells deficient in NEMO/IKKgamma, thereby suggesting an essential role of an intact IKK complex in this process. Our results suggest that HHV8 vFLIP might contribute to the persistent NF-kappaB activation observed in PEL cells by associating with and stimulating the activity of the cellular IKK complex.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1074/jbc.M110480200 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Wilms' tumor 1 (WT1) antigen is overexpressed in Kaposi Sarcoma and is regulated by KSHV vFLIP.
PLoS Pathog
January 2024
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, United States of America.
In people living with HIV, Kaposi Sarcoma (KS), a vascular neoplasm caused by KS herpesvirus (KSHV/HHV-8), remains one of the most common malignancies worldwide. Individuals living with HIV, receiving otherwise effective antiretroviral therapy, may present with extensive disease requiring chemotherapy. Hence, new therapeutic approaches are needed.
View Article and Find Full Text PDFActivation of glucocorticoid receptor signaling inhibits KSHV-induced inflammation and tumorigenesis.
mBio
January 2024
Cancer Virology Program, University of Pittsburgh Medical Center Hillman Cancer Center, Pittsburgh, Pennsylvania, USA.
Kaposi's sarcoma (KS) is the most common cancer in HIV-infected patients caused by Kaposi's sarcoma-associated herpesvirus (KSHV) infection. Hyperinflammation is the hallmark of KS. In this study, we have shown that KSHV mediates hyperinflammation by inducing IL-1α and suppressing IL-1Ra.
View Article and Find Full Text PDFKSHV hijacks FoxO1 to promote cell proliferation and cellular transformation by antagonizing oxidative stress.
J Med Virol
March 2023
Cancer Virology Program, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Reactive oxygen species (ROS) are a group of a highly short-lived molecules that control diverse behaviors of cells. Normal cells maintain ROS balance to ensure their functions. Because of oncogenic stress, cancer cells often have excessive ROS, also known as oxidative stress, which are often counteracted by enhanced antioxidant systems to maintain redox homeostasis.
View Article and Find Full Text PDFCRISPR screens identify novel regulators of cFLIP dependency and ligand-independent, TRAIL-R1-mediated cell death.
Cell Death Differ
May 2023
Department of Microbiology-Immunology, Northwestern University, Feinberg School of Medicine, Tarry 6-735, Chicago, IL, 60611, USA.
Kaposi's sarcoma-associated herpesvirus (KSHV) causes primary effusion lymphoma (PEL). PEL cell lines require expression of the cellular FLICE inhibitory protein (cFLIP) for survival, although KSHV encodes a viral homolog of this protein (vFLIP). Cellular and viral FLIP proteins have several functions, including, most importantly, the inhibition of pro-apoptotic caspase 8 and modulation of NF-κB signaling.
View Article and Find Full Text PDFNm23-H1 induces apoptosis in primary effusion lymphoma cells via inhibition of NF-κB signaling through interaction with oncogenic latent protein vFLIP K13 of Kaposi's sarcoma-associated herpes virus.
Cell Oncol (Dordr)
October 2022
Department of Biotechnology, Siksha Bhabana, Visva Bharati, Santiniketan, Bolpur, India.
Background: Primary effusion lymphoma (PEL) is an aggressive form of non-Hodgkin lymphoma of B cells caused by Kaposi's Sarcoma-associated Herpes Virus (KSHV). KSHV encoded latent and lytic antigens promote oncogenic transformation and evade apoptosis through the modulation of various host cellular signaling pathways. Nm23-H1 is a known metastatic suppressor whose expression inversely correlates with the metastatic potential of different cancers.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!