Sequence requirements of ATF2 and CREB binding to the human T-cell leukemia virus type 1 LTR R region.
We have identified crucial transcription factor contact sites within the distal portion of the HTLV-1 LTR R region. Single base substitutions within this region greatly reduce formation of a complex which we previously described as a 70-kDa nuclear protein interacting with a CREB-like protein. Comparison of published sequences of HTLV-1 isolates obtained from scattered geographic locations revealed that clustered mutations in an 8-base segment near the U5 junction do, in fact, occur naturally. A single base substitution corresponding to a common naturally occurring mutation was introduced into the R region of an HTLV-1-LTR Cat construct. This resulted in derepression of the promoter in a cell line expressing high levels of the R region binding complex when compared to the wild-type LTR promoter. Affinity purification and electrophoretic mobility super-shift analysis identified a dominant 70-kDa DNA binding protein as ATF-2. Phosphorylated ATF-2 apparently interacts with CREB to form this downstream complex.
Xu
X
X
Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, California 92037, USA.
Kang
S H
SH
Heidenreich
O
O
Brown
D A
DA
Nerenberg
M I
MI
D051698:Activating Transcription Factor 2; D001483:Base Sequence; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004279:DNA, Viral / Q000235:genetics* / Q000378:metabolism; D015490:HTLV-I Infections / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D008745:Methylation; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010766:Phosphorylation; D017354:Point Mutation / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
C497105:ATF2 protein, human; D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D004279:DNA, Viral; D014157:Transcription Factors