The K-bZIP Protein from Kaposi's Sarcoma-Associated Herpesvirus Interacts with p53 and Represses Its Transcriptional Activity

Park, Junsoo; Seo, Taegun; Hwang, Seungmin; Lee, Daeyoup; Gwack, Yousang; Choe, Joonho

doi:10.1128/jvi.74.24.11977-11982.2000

Cited by 73 publications

(63 citation statements)

References 33 publications

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“…Typically, the tumor response to chemotherapy is dependent upon functional p53. However, an in-depth analysis of p53 function in PEL has been missing, because multiple proteins of the PEL-associated human tumor virus KSHV were shown to inhibit p53 in ectopic expression experiments (27,31,48,55,61,62), thus asserting the dogma that all DNA tumor viruses inactivate p53. If this were true, the presence of KSHV would severely limit the treatment options for PEL and other KSHV-associated cancers.…”

Section: Discussionmentioning

confidence: 99%

“…How, then, can we reconcile these data with reports demonstrating disruption of p53 signaling by lytic and latent KSHV viral proteins? KSHV lytic proteins have been shown to inhibit p53 function through coactivator sequestration (Rta/ORF50) (18,31), repression of ATM-mediated DNA damage signaling (v-IRF) (62), or other unknown mechanisms (K-bZIP) (48). Neither Rta/ORF50, K-bZIP, nor vIRF-1 is expressed during latency in PEL (26).…”

Section: Discussionmentioning

confidence: 99%

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Functional p53 Signaling in Kaposi's Sarcoma-Associated Herpesvirus Lymphomas: Implications for Therapy

Petre

Sin

Dittmer

2007

J Virol

111

117

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The Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) is associated with Kaposi's sarcoma (KS) as well as primary effusion lymphomas (PEL). The expression of viral proteins capable of inactivating the p53 tumor suppressor protein has been implicated in KSHV oncogenesis. However, DNA-damaging drugs such as doxorubicin are clinically efficacious against PEL and KS, suggesting that p53 signaling remains intact despite the presence of KSHV. To investigate the functionality of p53 in PEL, we examined the response of a large number of PEL cell lines to doxorubicin. Two out of seven (29%) PEL cell lines harbored a mutant p53 allele (BCBL-1 and BCP-1) which led to doxorubicin resistance. In contrast, all other PEL containing wild-type p53 showed DNA damage-induced cell cycle arrest, p53 phosphorylation, and p53 target gene activation. These data imply that p53-mediated DNA damage signaling was intact. Supporting this finding, chemical inhibition of p53 signaling in PEL led to doxorubicin resistance, and chemical activation of p53 by the Hdm2 antagonist Nutlin-3 led to unimpaired induction of p53 target genes as well as growth inhibition and apoptosis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Functional p53 Signaling in Kaposi's Sarcoma-Associated Herpesvirus Lymphomas: Implications for Therapy

Petre

Sin

Dittmer

2007

J Virol

111

117

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“…Previous reports showed that latency-associated nuclear protein 1 (LANA1), K-bZIP, and vIRF3/LANA2 of KSHV interact with p53 and that these interactions result in the repression of p53-mediated transcription and apoptosis (3,16,21). Recently, Rivas et al (21) reported that KSHV LANA2 is a B-cell-specific latent viral protein and that it inhibits p53.…”

Section: Vol 75 2001mentioning

confidence: 99%

Viral Interferon Regulatory Factor 1 of Kaposi's Sarcoma-Associated Herpesvirus Binds to p53 and Represses p53-Dependent Transcription and Apoptosis

Seo

Park

Lee

et al. 2001

J Virol

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106

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Kaposi's sarcoma-associated herpesvirus (KSHV) is related to the development of Kaposi's sarcoma. Open reading frame K9 of KSHV encodes viral interferon regulatory factor 1 (vIRF1), which functions as a repressor of interferon-and IRF1-mediated signal transduction. In addition, vIRF1 acts as an oncogene to induce cellular transformation. Here we show that vIRF1 directly associates with the tumor suppressor p53 and represses its functions. The vIRF1 interaction domains of p53 are the DNA binding domain (amino acids [aa] 100 to 300) and the tetramerization domain (aa 300 to 393). p53 interacts with the central region (aa 152 to 360) of vIRF1. vIRF1 suppresses p53-dependent transcription and deregulates its apoptotic activity. These results suggest that vIRF1 may regulate cellular function by inhibiting p53.

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“…13,14) pISRE-Luc contains interferon stimulated response elements, pG-13-Luc contains synthetic p53 response elements. 15,16) Plasmid cytomegalovirus (pCMV)-RL (Renilla luciferase) was used to evaluate the control transcription. We found that AIF deregulated AP-1-and NF-kB-dependent transcriptions (Fig.…”

Section: Alpinumisoflavone Inhibits the Cell Viabilitymentioning

confidence: 99%

Alpinumisoflavone Induces Apoptosis and Suppresses Extracellular Signal-Regulated Kinases/Mitogen Activated Protein Kinase and Nuclear Factor-.KAPPA.B Pathways in Lung Tumor Cells

Namkoong

Kim

Jang

et al. 2011

Biological & Pharmaceutical Bulletin

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The extracellular signal-regulated kinase/mitogen activated protein kinase (ERK/MAPK) signaling cascade mediates the transduction of growth promoting signals such as growth factors, cytokines and proto-oncogenes through the activation of RAS, which leads to the activation of RAF (mitogen activated protein kinase kinase kinase, MAP3K) and then to activation of MEK (mitogen activated protein kinase kinase, MAP2K). MEK then phosphorylates and activates ERK (MAP kinase), and finally ERK activates the transcription factors FOS and JUN for the biological outcome.1) The ERK/MAPK signaling pathway not only promotes cell proliferation but also mediates cell survival, and ERK/MAPK signaling is up-regulated in cancer cells. Hence, ERK/MAPK signaling is a good target for cancer therapy, and several ERK/MAPK kinase signaling inhibitors have been developed for cancer therapy. 1,2)The nuclear factor-kB (NF-kB) signaling pathway plays major roles in inflammation, cell adhesion, differentiation and apoptosis.3) NF-kB signaling is tightly regulated by the cellular localization of NF-kB. Before activation, NF-kB is associated with the inhibitory kappa B (IkB) protein and localized in the cytoplasm. During activation, IkB kinase (IKK) phosphorylates IkB protein and ubiquitinates IkB for degradation. This process releases NF-kB protein, allowing the NF-kB to be translocated into the nucleus. The nuclear NF-kB binds to a specific sequence (kB element) and activates the transcription of target genes.3) Constitutive NF-kB activation has been observed in a wide variety of cancers, indicating that NF-kB signaling is critical for the initiation and progression of human cancers. 4,5) Therefore, the NF-kB signaling pathway and the ERK/MAPK kinase pathway are good targets for cancer therapies. 4,5) Plants from the genus Erythrina have a significant history of medicinal use for the treatment of diseases such as female fertility, stomach pain and gonorrhea, and Erythrina species are well known for their alkaloid and flavonoid contents. 6)Erythrina lysistemon is native to Africa and contains many prenylated flavonoids. 6) Alpinumisoflavone (AIF) is isolated from Erythrina lysistemon and little is known about its biological functions. Alpinumisoflavone is reported to inhibit mouse brain monoamine oxidase in vitro, 7) and it has a weak inhibitory effect on human protein tyrosine phosphatase 1B. 8)Recently, AIF and its derivative, methylalpinumisoflavone, have been shown to inhibit hypoxia inducible factor-1 (HIF-1) activation.9) Here we report that AIF induces the apoptosis of lung tumor cells and the apoptosis induced by AIF may be via deregulating both the ERK/MAPK and NF-kB pathways. MATERIALS AND METHODS Plant MaterialThe stem bark of Erythrina lysistemon was collected in Buea, Cameroon, in July 2003 and identified by Zacharias Tanee Fomum at the University of Yaoundé I (Yaoundé, Cameroon). A voucher specimen (No. 0005) was deposited at the Department of Botany, Yaoundé I University, Cameroon.Extraction and Isolation The dried and ground stem...

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The K-bZIP Protein from Kaposi's Sarcoma-Associated Herpesvirus Interacts with p53 and Represses Its Transcriptional Activity

Cited by 73 publications

References 33 publications

Functional p53 Signaling in Kaposi's Sarcoma-Associated Herpesvirus Lymphomas: Implications for Therapy

Functional p53 Signaling in Kaposi's Sarcoma-Associated Herpesvirus Lymphomas: Implications for Therapy

Viral Interferon Regulatory Factor 1 of Kaposi's Sarcoma-Associated Herpesvirus Binds to p53 and Represses p53-Dependent Transcription and Apoptosis

Alpinumisoflavone Induces Apoptosis and Suppresses Extracellular Signal-Regulated Kinases/Mitogen Activated Protein Kinase and Nuclear Factor-.KAPPA.B Pathways in Lung Tumor Cells

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