The Ubiquitin System and Kaposi’s Sarcoma-Associated Herpesvirus

Ashizawa, A; Higashi, Chizuka; Masuda, Kazuki; Ohga, Rie; Taira, Takahiro; Fujimuro, Masahiro

doi:10.3389/fmicb.2012.00066

Cited by 23 publications

(27 citation statements)

References 89 publications

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“…In fact, KSHV targets NF-κB signaling to influence gene expression and apoptosis. KSHV-encoded v-FLIP, K15, v-GPCR, K1 and K7 activate NF-κB signaling to achieve antiapoptosis in KSHV-infected cells, including PEL cells (4,6). Therefore, DAT-mediated destabilization of TRAF6 induces stabilization of IκBα and the subsequent inhibition of NF-κB signaling, which in turn may result in apoptosis of PEL cells.…”

Section: Discussionmentioning

confidence: 99%

“…Total RNA was purified and extracted from 1x10 6 cells using an Illustra RNAspin mini RNA Isolation kit (GE Healthcare, Buckinghamshire, uK). First-strand cDNA was synthesized from 20 ng of total RNA using a ReverTra Ace qPCR RT kit (Toyobo, Osaka, Japan).…”

Section: Reverse Transcription-polymerase Chain Reaction (Rt-pcr)mentioning

confidence: 99%

“…BC3 cells (1x10 6 ) were lysed in 0.2 ml of buffer containing 50 mm Tris-HCl (pH 7.6), 1 mm mgCl 2 , 0.1 mm EDTA, 1% glycerol, 1 mm DTT, 0.2 mm ATP, 0.2% NP-40, and homogenized with 27 G needles and 1 ml disposable syringes. The chymotrypsin-like activity of the proteasome in cell lysate was assessed with the fluorogenic peptide, Suc-Leu-Leu-Val-Tyr-4-methylcoumaryl-7-amide (mCA) (Peptide Institute, Osaka, Japan).…”

Section: Reverse Transcription-polymerase Chain Reaction (Rt-pcr)mentioning

confidence: 99%

“…LANA is required for the replication and maintenance of viral DNA, and contributes to KSHV-associated oncogenesis through interaction with cellular molecules, such as p53, Rb and GSK-3. These viral proteins and RNA manipulate cellular signaling pathways, including nuclear factor-κB (NF-κB), Akt, Wnt and Erk, to maintain the malignant phenotype and ensure PEL cell survival (4)(5)(6). Especially, NF-κB signaling is constitutively activated in KSHV-infected PEL cells to facilitate antiapoptosis and growth (7)(8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

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Diallyl trisulfide induces apoptosis by suppressing NF-κB signaling through destabilization of TRAF6 in primary effusion lymphoma

Shigemi

Furukawa

Hosokawa

et al. 2015

International Journal of Oncology

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Abstract. The allyl sulfides, including diallyl sulfide (DAS), diallyl disulfide (DAD), and diallyl trisulfide (DAT), contained in garlic and members of the Allium family, have a variety of pharmacological activities. Therefore, allyl sulfides have been evaluated as potential novel chemotherapeutic agents. Here, we found that DAT inhibited nuclear factor-κB (NF-κB) signaling and induced apoptosis in primary effusion lymphoma (PEL), a subtype of non-Hodgkin's B-cell lymphoma caused by Kaposi's sarcoma-associated herpesvirus (KSHV). We examined the cytotoxic effects of DAS, DAD and DAT on PEL cells. DAT significantly reduced the viability of PEL cells compared with uninfected B-lymphoma cells, and induced the apoptosis of PEL cells by activating caspase-9. DAT induced stabilization of IκBα, and suppressed NF-κB transcriptional activity in PEL cells. We examined the mechanism underlying DAT-mediated IκBα stabilization. The results indicated that DAT stabilized IκBα by inhibiting the phosphorylation of IκBα by the IκB kinase (IKK) complex. Furthermore, DAT induced proteasomal degradation of TRAF6, and DAT suppressed IKKβ-phosphorylation through downregulation of TRAF6. It is known that activation of NF-κB is essential for survival of PEL cells. In fact, the NF-κB inhibitor BAY11-7082 induced apoptosis in PEL cells. In addition, DAT suppressed the production of progeny virus from PEL cells. The administration of DAT suppressed the development of PEL cells and ascites in SCID mice xenografted with PEL cells. These findings provide evidence that DAT has antitumor activity against PEL cells in vitro and in vivo, suggesting it to be a novel therapeutic agent for the treatment of PEL. IntroductionPrimary effusion lymphoma (PEL, also termed body-cavitybased lymphoma) is a malignant B-cell lymphoma caused by Kaposi's sarcoma-associated herpesvirus (KSHV, also named HHV-8) in immunosuppressed individuals, such as AIDS patients or those that have undergone organ transplantation (1,2). PEL is a subtype of non-Hodgkin's lymphoma and is characterized by lymphomatous effusions of pleural and abdominal cavities. KSHV is a rhadinovirus of the γ-herpesvirus subfamily and is closely related to herpesvirus Saimiri and Epstein-Barr virus (EBV). KSHV is the causative agent of Kaposi's sarcoma and AIDS-related lymphoproliferative disorders, such as PEL and multicentric Castleman's disease (3). Similar to other herpesviruses, KSHV has two life cycles (latency and lytic replication). The KSHV genome circularizes and forms a double-stranded DNA, the episome, in the nucleus of PEL cells during latent infection. To establish a latent infection, KSHV expresses several viral genes, including latency-associated nuclear antigen (LANA), v-FLIP, v-cyclin, kaposin and microRNAs, in PEL cells. LANA is required for the replication and maintenance of viral DNA, and contributes to KSHV-associated oncogenesis through interaction with cellular molecules, such as p53, Rb and GSK-3. These viral proteins and RNA manipulate cellular signaling pathways, includ...

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Section: Discussionmentioning

confidence: 99%

Section: Reverse Transcription-polymerase Chain Reaction (Rt-pcr)mentioning

confidence: 99%

Section: Reverse Transcription-polymerase Chain Reaction (Rt-pcr)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Diallyl trisulfide induces apoptosis by suppressing NF-κB signaling through destabilization of TRAF6 in primary effusion lymphoma

Shigemi

Furukawa

Hosokawa

et al. 2015

International Journal of Oncology

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“…Kaposi sarcoma‐associated herpesvirus modulates the ubiquitination pathway through LANA binding to Fbw7/Sel10 and suppressing NICD degradation (Figure C). In addition, increased expression of Hey‐1 is stabilized by LANA (Figure B).…”

Section: Introductionmentioning

confidence: 99%

Deregulation of the Notch pathway as a common road in viral carcinogenesis

Vázquez-Ulloa

Lizano

Sjöqvist

et al. 2018

Reviews in Medical Virology

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The Notch pathway is a conserved signaling pathway and a form of direct cell-cell communication related to many biological processes during development and adulthood. Deregulation of the Notch pathway is involved in many diseases, including cancer. Almost 20% of all cancer cases have an infectious etiology, with viruses responsible for at least 1.5 million new cancer cases per year. Seven groups of viruses have been classified as oncogenic: hepatitis B and C viruses (HBV and HCV respectively), Epstein-Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV), human T lymphotropic virus (HTLV-1), human papillomavirus (HPV), and Merkel cell polyomavirus (MCPyV). These viruses share the ability to manipulate a variety of cell pathways that are critical in proliferation and differentiation, leading to malignant transformation. Viral proteins interact directly or indirectly with different members of the Notch pathway, altering their normal function. This review focuses exclusively on the direct interactions of viral oncoproteins with Notch elements, providing a deeper understanding of the dual behavior of the Notch pathway as activator or suppressor of neoplasia in virus-related cancers.

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Viral Manipulations of the Cullin-RING Ubiquitin Ligases

Liu

Tan

2020

Advances in Experimental Medicine and Biology

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The Ubiquitin System and Kaposi’s Sarcoma-Associated Herpesvirus

Cited by 23 publications

References 89 publications

Diallyl trisulfide induces apoptosis by suppressing NF-κB signaling through destabilization of TRAF6 in primary effusion lymphoma

Diallyl trisulfide induces apoptosis by suppressing NF-κB signaling through destabilization of TRAF6 in primary effusion lymphoma

Deregulation of the Notch pathway as a common road in viral carcinogenesis

Viral Manipulations of the Cullin-RING Ubiquitin Ligases

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