Human T-lymphotropic virus type 1 p30(II) regulates gene transcription by binding CREB binding protein/p300.
The highly conserved coadapters CREB binding protein (CBP) and p300 form complexes with CREB as well as other DNA binding transcription factors to modulate chromatin remodeling and thus transcription. Human T-lymphotropic virus type 1 (HTLV-1) transcription is controlled, in part, by the CREB/ATF family of transcription factors which bind promoter sequences and function as complexes with the viral oncogenic protein Tax. We have reported that the nuclear localizing protein p30(II) of HTLV-1 functions as a transcription factor, differentially modulates CREB-responsive promoters, and is critical for maintenance of proviral loads in rabbits. In this study, we tested whether p30(II) directly interacts with CBP/p300 to modulate gene transcription. Gal4(BD)-p30(II)-mediated transactivation was enhanced following exogenous expression of p300 and was competitively repressed by the p300 binding protein, adenovirus E1A, and E1ACR2 (mutated for retinoblastoma binding but retaining p300 binding). In contrast, E1ACR1 (mutated for p300 binding) failed to alter Gal4(BD)-p30(II)-mediated transactivation. In addition, Gal4(BD)-p30(II)-mediated transactivation was competitively inhibited by the cotransfection of CMV-p30(II)-HA and CMV-Tax but could be rescued by exogenous p300. Importantly, we demonstrate that p30(II) colocalizes with p300 in cell nuclei and directly binds to CBP/p300 in cells. Deletion mutants of CBP/p300 were used to localize the site critical for binding p30(II) to a highly conserved KIX region. DNA binding assays confirmed the interference of p30(II) with the assembly of CREB-Tax-p300/CBP multiprotein complexes on 21-bp repeat oligonucleotides in vitro. Collectively, our results demonstrate that CBP/p300 is a cellular protein target for HTLV-1 p30(II) and mediates its transcriptional effects in vivo.
Zhang
W
W
Center for Retrovirus Research and Department of Veterinary Biosciences, The Arthur James Cancer Hospital and Research Institute, The Ohio State University, Columbus, Ohio 43210, USA.
Nisbet
J W
JW
Albrecht
B
B
Ding
W
W
Kashanchi
F
F
Bartoe
J T
JT
Lairmore
M D
MD
D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D012191:Retroviridae Proteins / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D017500:Adenovirus E1A Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D009687:Nuclear Proteins; D012191:Retroviridae Proteins; D015534:Trans-Activators; C072814:tof protein, Human T-lymphotropic virus 1