Transcriptional regulation of the bovine leukemia virus promoter by the cyclic AMP-response element modulator tau isoform.
Bovine leukemia virus (BLV) expression is controlled at the transcriptional level through three Tax(BLV)-responsive elements (TxREs) responsive to the viral transactivator Tax(BLV). The cAMP-responsive element (CRE)-binding protein (CREB) has been shown to interact with CRE-like sequences present in the middle of each of these TxREs and to play critical transcriptional roles in both basal and Tax(BLV)-transactivated BLV promoter activity. In this study, we have investigated the potential involvement of the cAMP-response element modulator (CREM) in BLV transcriptional regulation, and we have demonstrated that CREM proteins were expressed in BLV-infected cells and bound to the three BLV TxREs in vitro. Chromatin immunoprecipitation assays using BLV-infected cell lines demonstrated in the context of chromatin that CREM proteins were recruited to the BLV promoter TxRE region in vivo. Functional studies, in the absence of Tax(BLV), indicated that ectopic CREMtau protein had a CRE-dependent stimulatory effect on BLV promoter transcriptional activity. Cross-link of the B-cell receptor potentiated CREMtau transactivation of the viral promoter. Further experiments supported the notion that this potentiation involved CREMtau Ser-117 phosphorylation and recruitment of CBP/p300 to the BLV promoter. Although CREB and Tax(BLV) synergistically transactivated the BLV promoter, CREMtau repressed this Tax(BLV)/CREB synergism, suggesting that a modulation of the level of Tax(BLV) transactivation through opposite actions of CREB and CREMtau could facilitate immune escape and allow tumor development.
Nguyên
Thi Lien-Anh
TL
Institut de Biologie et de Médecine Moléculaires, Laboratoire de Virologie Moléculaire, Université Libre de Bruxelles, Rue des Profs Jeener et Brachet 12, 6041 Gosselies, Belgium.
de Walque
Stéphane
S
Veithen
Emmanuelle
E
Dekoninck
Ann
A
Martinelli
Valérie
V
de Launoit
Yvan
Y
Burny
Arsène
A
Harrod
Robert
R
Van Lint
Carine
C
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D003432:Cross-Linking Reagents / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D051786:Cyclic AMP Response Element Modulator / Q000737:chemistry / Q000235:genetics*; D016356:Gene Products, tax / Q000378:metabolism; D001909:Leukemia Virus, Bovine / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D020033:Protein Isoforms; D014158:Transcription, Genetic
D003432:Cross-Linking Reagents; D016356:Gene Products, tax; D020033:Protein Isoforms; D051786:Cyclic AMP Response Element Modulator; D000242:Cyclic AMP