Specific TATAA and bZIP requirements suggest that HTLV-I Tax has transcriptional activity subsequent to the assembly of an initiation complex.
BACKGROUND
Human T-cell leukemia virus type I (HTLV-I) Tax protein is a transcriptional regulator of viral and cellular genes. In this study we have examined in detail the determinants for Tax-mediated transcriptional activation.


RESULTS
Whereas previously the LTR enhancer elements were thought to be the sole Tax-targets, herein, we find that the core HTLV-I TATAA motif also provides specific responsiveness not seen with either the SV40 or the E1b TATAA boxes. When enhancer elements which can mediate Tax-responsiveness were compared, the authentic HTLV-I 21-bp repeats were found to be the most effective. Related bZIP factors such as CREB, ATF4, c-Jun and LZIP are often thought to recognize the 21-bp repeats equivalently. However, amongst bZIP factors, we found that CREB, by far, is preferred by Tax for activation. When LTR transcription was reconstituted by substituting either kappaB or serum response elements in place of the 21-bp repeats, Tax activated these surrogate motifs using surfaces which are different from that utilized for CREB interaction. Finally, we employed artificial recruitment of TATA-binding protein to the HTLV-I promoter in "bypass" experiments to show for the first time that Tax has transcriptional activity subsequent to the assembly of an initiation complex at the promoter.


CONCLUSIONS
Optimal activation of the HTLV-I LTR by Tax specifically requires the core HTLV-I TATAA promoter, CREB and the 21-bp repeats. In addition, we also provide the first evidence for transcriptional activity of Tax after the recruitment of TATA-binding protein to the promoter.
Department of Biochemistry, The University of Hong Kong, Pokfulam, Hong Kong, China. ypching@hkucc.hku.hk
Yick-Pang
YP
Ching
Abel C S
AC
Chun
King-Tung
KT
Chin
Zhi-Qing
ZQ
Zhang
Kuan-Teh
KT
Jeang
Dong-Yan
DY
Jin
D000951:Antigens, Neoplasm / Q000235:genetics*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics; D016356:Gene Products, tax / Q000378:metabolism*; D006649:Histocompatibility Antigens / Q000235:genetics*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics*; D010442:Peptide Chain Initiation, Translational; D011401:Promoter Regions, Genetic; D016601:RNA-Binding Proteins / Q000235:genetics*; D012091:Repetitive Sequences, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic
C105242:ALYREF protein, human; D000951:Antigens, Neoplasm; D017362:Cyclic AMP Response Element-Binding Protein; D016356:Gene Products, tax; D006649:Histocompatibility Antigens; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C029237:tumor-associated transplantation antigen