Latency-associated nuclear antigen of Kaposi's sarcoma-associated herpesvirus (human herpesvirus-8) binds ATF4/CREB2 and inhibits its transcriptional activation activity.
Latency-associated nuclear antigen (LANA), encoded by ORF 73 of Kaposi's sarcoma-associated herpesvirus (KSHV; human herpesvirus-8), may play an important role in the persistence of the viral episome by tethering it to host chromosomes during mitosis. It also has been suggested from its amino acid sequence features that LANA may have transcription-regulatory activity. Here, it is reported that LANA interacts with activating transcription factor (ATF) 4/cAMP response element-binding protein (CREB) 2, a member of the ATF/CREB family of transcription factors, and represses the transcriptional activation activity of ATF4/CREB2. Repression by LANA is independent of the DNA-binding ability of ATF4/CREB2, since LANA also represses transactivation of ATF4/CREB2 fused to the GAL4 DNA-binding domain and does not affect the DNA-binding ability of ATF4/CREB2 in an electrophoretic mobility shift assay. The putative leucine zipper domain of LANA is required for binding to the relatively conserved basic region/leucine zipper domain (bZIP) of ATF4/CREB2, suggesting that the interaction may involve leucine zipper dimerization.
Lim
Chunghun
C
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejeon 305-701, Korea1.
Sohn
Hekwang
H
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejeon 305-701, Korea1.
Gwack
Yousang
Y
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejeon 305-701, Korea1.
Choe
Joonho
J
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Taejeon 305-701, Korea1.
D051701:Activating Transcription Factor 4; D000956:Antigens, Viral / Q000502:physiology; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D006367:HeLa Cells; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D009687:Nuclear Proteins / Q000502:physiology*; D010957:Plasmids / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*; D015533:Transcriptional Activation; D017735:Virus Latency / Q000502:physiology; D014779:Virus Replication
C497109:ATF4 protein, human; D000956:Antigens, Viral; D009687:Nuclear Proteins; D014157:Transcription Factors; C109540:latency-associated nuclear antigen; D051701:Activating Transcription Factor 4