Ets-1-dependent expression of vascular endothelial growth factor receptors is activated by latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus through interaction with Daxx

Yuko Murakami, Satoshi Yamagoe, Kohji Noguchi, Yutaka Takebe, Naoko Takahashi, Yoshimasa Uehara, Hidesuke Fukazawa

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Vascular endothelial growth factor (VEGF) and its receptors are highly expressed in Kaposi's sarcoma (KS) lesion and play a key role in angiogenesis. Latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) has multiple functions related to viral latency and KSHV-induced oncogenesis. In this report, we have identified Daxx as a LANA-binding protein by co-immunoprecipitation analysis of HeLa cells stably expressing LANA. LANA associated with Daxx in a PEL cell line infected with KSHV. LANA and Daxx also bound in vitro, suggesting direct interaction. From the results of binding assays, a region containing the Glu/Asp-rich domain within LANA, and a central region including the second paired amphipathic helix within Daxx contributed to the interaction. To address the physiological significance of this interaction, we focused on a Daxx-mediated VEGF receptor gene regulation. We found that Daxx repressed Ets-1-dependent Flt-1/VEGF receptor-1 gene expression, and that LANA inhibited the repression by Daxx in a reporter assay. Analyses of flow cytometry and real-time PCR revealed that expression of VEGF receptor-1 and -2 in LANA-expressing human umbilical vein endothelial cells (HUVECs) significantly increased. Co-immunoprecipitation and immunoblotting experiments suggested that LANA-bound Daxx to inhibit the interaction between Daxx and Ets-1. Chromatin immunoprecipitation assays showed that Daxx associated with VEGF receptor-1 promoter in HUVECs, and that LANA expression reduced this association. These results suggested that LANA contributes to a high expression of VEGF receptors in KS lesion by interfering with the interaction between Daxx and Ets-1.

Original languageEnglish
Pages (from-to)28113-28121
Number of pages9
JournalJournal of Biological Chemistry
Volume281
Issue number38
DOIs
Publication statusPublished - 2006 Sep 22
Externally publishedYes

Fingerprint

Human Herpesvirus 8
Vascular Endothelial Growth Factor Receptor
Vascular Endothelial Growth Factor Receptor-1
Assays
Kaposi's Sarcoma
Endothelial cells
Human Umbilical Vein Endothelial Cells
Immunoprecipitation
Gene expression
latency-associated nuclear antigen
Virus Latency
Vascular Endothelial Growth Factor Receptor-2
Flow cytometry
Chromatin Immunoprecipitation
HeLa Cells
Immunoblotting
Chromatin
Real-Time Polymerase Chain Reaction
Carrier Proteins
Flow Cytometry

ASJC Scopus subject areas

  • Biochemistry

Cite this

Ets-1-dependent expression of vascular endothelial growth factor receptors is activated by latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus through interaction with Daxx. / Murakami, Yuko; Yamagoe, Satoshi; Noguchi, Kohji; Takebe, Yutaka; Takahashi, Naoko; Uehara, Yoshimasa; Fukazawa, Hidesuke.

In: Journal of Biological Chemistry, Vol. 281, No. 38, 22.09.2006, p. 28113-28121.

Research output: Contribution to journalArticle

Murakami, Yuko ; Yamagoe, Satoshi ; Noguchi, Kohji ; Takebe, Yutaka ; Takahashi, Naoko ; Uehara, Yoshimasa ; Fukazawa, Hidesuke. / Ets-1-dependent expression of vascular endothelial growth factor receptors is activated by latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus through interaction with Daxx. In: Journal of Biological Chemistry. 2006 ; Vol. 281, No. 38. pp. 28113-28121.
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AU - Takebe, Yutaka

AU - Takahashi, Naoko

AU - Uehara, Yoshimasa

AU - Fukazawa, Hidesuke

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