PMID- 9018122
OWN - NLM
STAT- MEDLINE
DCOM- 19970227
LR  - 20220408
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 14
IP  - 3
DP  - 1997 Jan 23
TI  - Human herpesvirus 6 (HHV-6) ORF-1 transactivating gene exhibits malignant 
      transforming activity and its protein binds to p53.
PG  - 359-67
AB  - The 357 amino acid open reading frame 1 (ORF-1), also designated DR7, within the 
      SalI-L fragment of human herpesvirus 6 (HHV-6) exhibited transactivation of the 
      human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) promoter 
      and increased HIV-1 replication (Kashanchi et al., Virology, 201, 95-106, 1994). 
      In the current study, the SalI-L transforming region was localized to the 
      SalI-L-SH subfragment. Several ORFs identified in SalI-L-SH by sequence analysis 
      were cloned into a selectable mammalian expression vector, pBK-CMV. Only pBK/ORF1 
      transformed NIH3T3 cells. Furthermore, cells expressing ORF-1 protein produced 
      fibrosarcomas when injected into nude mice, whereas control cells, expressing 
      either no ORF-1 protein or C-terminal truncated (after residue 172) ORF-1 
      protein, were not tumorigenic. Western blot analysis of proteins extracted from 
      the tumors revealed ORF-1 protein. Additional studies indicated that ORF-1 was 
      expressed in HHV-6-infected human T-cells by 18 h. Co-immunoprecipitation 
      experiments showed that ORF-1 protein bound to tumor suppressor protein p53, and 
      the ORF-1 binding domain on p53 was located between residues 28 and 187 of p53, 
      overlapping with the specific DNA binding domain. Functional studies showed that 
      p53-activated transcription was inhibited in ORF-1, but not in truncated ORF-1, 
      expressing cells. Importantly, the truncated ORF-1 mutant also failed to cause 
      transformation. Analysis of several human tumors by PCR revealed ORF-1 DNA 
      sequences in some angioimmunoblastic lymphadenopathies, Hodgkin's and 
      non-Hodgkin's lymphomas and glioblastomas. The detection of ORF-1 sequences in 
      human tumors, while not proof per se, is a prerequisite for establishing its role 
      in tumor development. Taken together, the results demonstrate that ORF-1 is an 
      HHV-6 oncogene that binds to and affects p53. The identification of both 
      transforming and transactivating activities within ORF-1 is a characteristic of 
      other viral oncogenes and is the first reported for HHV-6.
FAU - Kashanchi, F
AU  - Kashanchi F
AD  - Laboratory of Molecular Virology, National Cancer Institute, National Institutes 
      of Health, Bethesda, Maryland 20892, USA.
FAU - Araujo, J
AU  - Araujo J
FAU - Doniger, J
AU  - Doniger J
FAU - Muralidhar, S
AU  - Muralidhar S
FAU - Hoch, R
AU  - Hoch R
FAU - Khleif, S
AU  - Khleif S
FAU - Mendelson, E
AU  - Mendelson E
FAU - Thompson, J
AU  - Thompson J
FAU - Azumi, N
AU  - Azumi N
FAU - Brady, J N
AU  - Brady JN
FAU - Luppi, M
AU  - Luppi M
FAU - Torelli, G
AU  - Torelli G
FAU - Rosenthal, L J
AU  - Rosenthal LJ
LA  - eng
GR  - CA 60577/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (ORF-1 protein, Human herpesvirus 6)
RN  - 0 (Trans-Activators)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - 0 (Viral Proteins)
SB  - IM
MH  - 3T3 Cells
MH  - Animals
MH  - Fibrosarcoma/genetics
MH  - Genes, Regulator/*physiology
MH  - Genetic Vectors
MH  - Humans
MH  - Mice
MH  - Mice, Nude
MH  - *Oncogenes
MH  - Trans-Activators/*genetics/*metabolism
MH  - *Transcriptional Activation
MH  - Transfection
MH  - Tumor Suppressor Protein p53/*metabolism
MH  - Viral Proteins/*genetics/*metabolism
EDAT- 1997/01/23 00:00
MHDA- 1997/01/23 00:01
CRDT- 1997/01/23 00:00
PHST- 1997/01/23 00:00 [pubmed]
PHST- 1997/01/23 00:01 [medline]
PHST- 1997/01/23 00:00 [entrez]
AID - 10.1038/sj.onc.1200840 [doi]
PST - ppublish
SO  - Oncogene. 1997 Jan 23;14(3):359-67. doi: 10.1038/sj.onc.1200840.