PMID- 8350410
OWN - NLM
STAT- MEDLINE
DCOM- 19930913
LR  - 20211203
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 67
IP  - 9
DP  - 1993 Sep
TI  - Activation of the human T-cell leukemia virus type I enhancer is mediated by 
      binding sites for Elf-1 and the pets factor.
PG  - 5522-8
AB  - Infection with human T-cell leukemia virus type I (HTLV-I) is associated with 
      adult T-cell lymphoma/leukemia. This disease occurs in only a small minority of 
      people infected with HTLV-I and manifests itself many years after infection. 
      Therefore, it appears that a fine balance exists between HTLV-I and the host 
      T-cell factors with which it interacts. HTLV-I encodes a transactivating protein, 
      Tax, which activates viral transcription via cellular mechanisms which are 
      incompletely understood. As viral gene expression is negligible during latency, 
      it is doubtful that Tax controls the initial transition to the replicative state. 
      Tax-independent cellular factors which control HTLV-I transcription, and 
      presumably latency, have received little study. Recently, the product of the 
      chicken proto-oncogene ets-1 has been shown to bind to the HTLV-I enhancer and 
      modestly activate transcription in certain cell types (S. C. Gitlin, R. Bosselut, 
      A. Gegonne, J. Ghysdael, and J. N. Brady, J. Virol. 65:5513-5523, 1991). However, 
      the functional significance of the ets-binding site in the intact enhancer has 
      not previously been shown. We now demonstrate that site-specific mutation of the 
      purine-rich ets-binding site significantly diminishes inducible enhancer 
      function, but not Tax response, in the human Jurkat T-cell line. Similarly, 
      mutation of the peri-ets (pets) site, not previously noted in the HTLV-I 
      enhancer, markedly inhibits inducible enhancer function but not Tax response. 
      Further, we show that the predominant protein binding the purine-rich HTLV-I 
      enhancer element in human T cells is not ets-1 but Elf-1, a member of the ets 
      family which is very similar to the Drosophila morphogen E74. Regulation of 
      HTLV-I through Elf-1/pets enhancer motifs resembles that seen with human 
      immunodeficiency virus type 2 (D. M. Markovitz, M. Smith, J. Hilfinger, M. C. 
      Hannibal, B. Petryniak, and G. J. Nabel, J. Virol. 66:5479-5484, 1992; J. M. 
      Leiden, C.-W. Wang, B. Petryniak, M. Smith, D. M. Markovitz, G. J. Nabel, and C. 
      B. Thompson, J. Virol. 66:5890-5897, 1992), another human pathogenic retrovirus 
      with a relatively long incubation period.
FAU - Clark, N M
AU  - Clark NM
AD  - Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 
      48109-0680.
FAU - Smith, M J
AU  - Smith MJ
FAU - Hilfinger, J M
AU  - Hilfinger JM
FAU - Markovitz, D M
AU  - Markovitz DM
LA  - eng
GR  - AI30924/AI/NIAID NIH HHS/United States
GR  - CA01479/CA/NCI NIH HHS/United States
GR  - T32AI07360/AI/NIAID NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Drosophila Proteins)
RN  - 0 (ETS1 protein, human)
RN  - 0 (Gene Products, tax)
RN  - 0 (MAS1 protein, human)
RN  - 0 (Oligonucleotide Probes)
RN  - 0 (Proto-Oncogene Mas)
RN  - 0 (Proto-Oncogene Protein c-ets-1)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-ets)
RN  - 0 (Transcription Factors)
RN  - 0 (grh protein, Drosophila)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Binding Sites
MH  - Cell Nucleus/drug effects/metabolism
MH  - Chickens
MH  - DNA-Binding Proteins/*metabolism
MH  - Drosophila/genetics
MH  - Drosophila Proteins
MH  - *Enhancer Elements, Genetic
MH  - *Gene Expression Regulation, Viral
MH  - Gene Products, tax/*metabolism
MH  - Genes, Viral
MH  - Human T-lymphotropic virus 1/*genetics/metabolism
MH  - Humans
MH  - Molecular Sequence Data
MH  - Oligonucleotide Probes
MH  - Proto-Oncogene Mas
MH  - Proto-Oncogene Protein c-ets-1
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-ets
MH  - Proto-Oncogenes
MH  - Restriction Mapping
MH  - TATA Box
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Transcription Factors/*metabolism
MH  - Tumor Cells, Cultured
PMC - PMC237955
EDAT- 1993/09/01 00:00
MHDA- 1993/09/01 00:01
PMCR- 1993/09/01
CRDT- 1993/09/01 00:00
PHST- 1993/09/01 00:00 [pubmed]
PHST- 1993/09/01 00:01 [medline]
PHST- 1993/09/01 00:00 [entrez]
PHST- 1993/09/01 00:00 [pmc-release]
AID - 10.1128/JVI.67.9.5522-5528.1993 [doi]
PST - ppublish
SO  - J Virol. 1993 Sep;67(9):5522-8. doi: 10.1128/JVI.67.9.5522-5528.1993.