Pyrrolidinium fullerene induces apoptosis by activation of procaspase-9 via suppression of Akt in primary effusion lymphoma

Watanabe, Tadashi; Nakamura, Shigeo; Ono, Takahiro; Ui, Sadaharu; Yagi, Syota; Kagawa, Hiroyasu; Watanabe, Hirotaka; Ohe, Tomoyuki; Mashino, Tadahiko; Fujimuro, Masahiro

doi:10.1016/j.bbrc.2014.07.068

Cited by 26 publications

(41 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For quantification of virus production, KSHV virions in culture supernatant were quantified as previously described 39, 40 . Briefly, iVero cells (iVero-WT, iVero-ΔORF34 or iVero-Revertant) were treated with 8 μg/mL of doxycycline and 1.5 mM of NaB for 48 hours to induce to lytic replication and production of recombinant KSHV, and culture supernatants were harvested.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Kaposi’s sarcoma-associated herpesvirus ORF34 is essential for late gene expression and virus production

Nishimura

Watanabe

Yagi

et al. 2017

Sci Rep

Self Cite

108

View full text Add to dashboard Cite

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. KSHV establishes a life-long infection in its host and alternates between a latent and lytic infection state. During lytic infection, lytic-related genes are expressed in a temporal manner and categorized as immediate early, early, and late gene transcripts. ORF34 is an early-late gene that interacts with several viral transcription-associated factors, however its physiological importance remains poorly understood. Here, we investigated the role of ORF34 during KSHV infection by generating ORF34-deficient KSHV, using a bacterial artificial chromosome system. Our results reveal that ORF34-deficient KSHV exhibited significantly attenuated late gene expression and viral production but did not affect viral DNA replication. ORF34 interacted with transcription factors ORF18, ORF24, ORF31, and ORF66, and a novel ORF34-interaction partner, ORF23. The C-terminal region of ORF34 was important for interaction with ORF24 and viral production. Our data support a model, in which ORF34 serves as a hub for recruiting a viral transcription complex to ORF24 to promote late viral gene expression.

show abstract

Section: Methodsmentioning

confidence: 99%

“…Western blots were performed as described previously 39, 41 . For pull-down assays, transfected 293T cells were lysed by HNTG buffer (20 mM HEPES (pH 7.9), 0.18 M NaCl, 0.1% NP-40, 0.1 mM EDTA, 10% Glycerol) 16 with protease inhibitors and sonicated.…”

Section: Methodsmentioning

confidence: 99%

Kaposi’s sarcoma-associated herpesvirus ORF34 is essential for late gene expression and virus production

Nishimura

Watanabe

Yagi

et al. 2017

Sci Rep

Self Cite

108

View full text Add to dashboard Cite

show abstract

“…For quantification of virus production, KSHV virions in culture supernatant were quantified as previously described (20, 40, 41). Briefly, iSLK and iVero cells (iSLK-WT, iSLK-ΔORF66, iVero-WT, or iVero-ΔORF66) were treated with Sodium Butyrate (NaB) and doxycycline (iSLK; NaB 0.75 mM/ Dox 4 μg/mL, iVero; NaB 1.5 mM/ Dox 8 μg/mL) for 72 hours to induce to lytic replication and production of recombinant KSHV, and culture supernatants were harvested.…”

Section: Methodsmentioning

confidence: 99%

Kaposi’s sarcoma-associated herpesvirus ORF66 is essential for late gene expression and virus production via interaction with ORF34

Watanabe

Nishimura

Izumi

et al. 2019

Preprint

Self Cite

View full text Add to dashboard Cite

25Kaposi's sarcoma-associated herpesvirus (KSHV) is closely 26 associated with B-cell and endothelial cell malignancies. After the initial 27 infection, KSHV retains its viral genome in the nucleus of the host cell and 28 establishes a lifelong latency. During lytic infection, KSHV encoded lytic-related 29 proteins are expressed in a sequential manner and are classified as immediate 30 early, early, and late gene transcripts. The transcriptional initiation of KSHV late 31 genes is thought to require the complex formation of the virus specific pre-32 initiation complex (vPIC), which may consist of at least 6 transcription factors 33 (ORF18, 24, 30, 31, 34, and 66). However, the functional role of ORF66 in vPIC 34 during KSHV replication remains largely unclear. Here, we generated ORF66-35 deficient KSHV using a BAC system to evaluate its role during viral replication. 36While ORF66-deficient KSHV demonstrated mainly attenuated late gene 37 expression and decreased viral production, viral DNA replication was 38 unaffected. CHIP analysis showed that ORF66 bound to the promoters of late 39 gene (K8.1), but did not to those of latent gene (ORF72), immediate early gene 40 (ORF16) and early gene (ORF46/47). Furthermore, we found that three highly 41 conserved C-X-X-C sequences and a conserved leucine-repeat in the C-42 terminal region of ORF66 were essential for interaction with ORF34 and viral 43 production. The interaction between ORF66 and ORF34 occurred in a zinc-44 dependent manner. Our data support a model, in which ORF66 serves as a 45 critical vPIC component to promote late viral gene expression and viral 46 production. 47 IMPORTANCE 49 KSHV ORF66, a late gene product, and vPIC are thought to contribute 50 significantly to late gene expression during the lytic replication. However, the 51 physiological importance of ORF66 in terms of viral replication and vPIC 52 formation remains poorly understood. Therfore, we generated a ORF66-53 deficient BAC clone and evaluated its viral replication. Results showed that 54 ORF66 played a critical role in virus production and the transcription of L genes. 55To our knowledge, this is the first report showing ORF66 function in virus 56 replication using ORF66-deficient KSHV. We also clarified that ORF66 57 interacted with the transcription start site of K8.1 gene, a late gene. 58 Furthermore, we identified the ORF34-binding motifs in the ORF66 C-terminus: 59 three C-X-X-C sequences and a leucine-repeat sequence, which are highly 60 conserved among -and -herpesviruses. Our study provides insights into the 61 regulatory mechanisms of not only the late gene expression of KSHV but also 62 those of other herpesviruses. 63 64 65 replication. Finally, the transcriptional products of L genes, contribute to viral 90 particle formation by its encoding viral structure proteins (15). 91The viral pre-initiation complex (vPIC) has recently been proposed to 92 regulate L gene expression(16). vPIC is composed of several viral proteins 93 conserved among -and -herpesviruses (17), and has f...

show abstract

“…106-113 Pyrrolidinium fullerene derivatives have been shown to induce mitochondrion- and caspase-dependent apoptosis through the generation of ROS in human promyeloleukaemia (HL-60) cells. 114 …”

Section: Anti Cancer Propertiesmentioning

confidence: 99%

Fullerenes in biology and medicine

et al. 2017

View full text Add to dashboard Cite

show abstract

Pyrrolidinium fullerene induces apoptosis by activation of procaspase-9 via suppression of Akt in primary effusion lymphoma

Cited by 26 publications

References 24 publications

Kaposi’s sarcoma-associated herpesvirus ORF34 is essential for late gene expression and virus production

Kaposi’s sarcoma-associated herpesvirus ORF34 is essential for late gene expression and virus production

Kaposi’s sarcoma-associated herpesvirus ORF66 is essential for late gene expression and virus production via interaction with ORF34

Fullerenes in biology and medicine

Contact Info

Product

Resources

About