Transcriptional coactivation of c-Jun by the KSHV-encoded LANA.
The Kaposi sarcoma-associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen (LANA) modulates viral and cellular gene expression, including interleukin 6 (IL-6), a growth factor for KSHV-associated diseases. LANA-driven IL-6 expression is dependent on the activator protein 1 (AP1) response element (RE) within the IL-6 promoter. We show that LANA activates the AP1 RE in a Jun-dependent fashion and that LANA enhances the transcriptional activity of a GAL4-Jun fusion protein. Coimmunoprecipitation studies documented a physical interaction between LANA and c-Jun in transiently transfected 293 cells as well as the KSHV-infected BCBL-1 primary effusion lymphoma (PEL) cell line. Taken together, these data indicate that LANA is a transcriptional coactivator of c-Jun. In addition, electrophoretic mobility shift assays demonstrated that LANA induces binding of a c-Jun-Fos heterodimer to the AP1 RE, but does not itself bind to the AP1 RE. RNA interference experiments confirmed that LANA activates the AP1 RE, stimulates binding of a c-Jun-Fos heterodimer to the AP1 RE, and induces expression of IL-6. These data indicate that LANA is a transcriptional coactivator of c-Jun, a function that may have implications for the pathogenesis of KSHV-associated diseases.
An
Jiabin
J
VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA.
Sun
Yiping
Y
Rettig
Matthew B
MB
D000956:Antigens, Viral; D001483:Base Sequence; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics; D020868:Gene Silencing; D019288:Herpesvirus 8, Human / Q000235:genetics*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics*; D011485:Protein Binding; D016760:Proto-Oncogene Proteins c-fos / Q000737:chemistry / Q000378:metabolism; D034622:RNA Interference; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection
D000956:Antigens, Viral; D004279:DNA, Viral; D015850:Interleukin-6; D009687:Nuclear Proteins; D016760:Proto-Oncogene Proteins c-fos; D018808:Transcription Factor AP-1; C109540:latency-associated nuclear antigen; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases