Transactivation of the fucosyltransferase VII gene by human T-cell leukemia virus type 1 Tax through a variant cAMP-responsive element.
Human T-cell leukemic virus type 1 (HTLV-1)-infected T cells express the fucosyltransferase (Fuc-T) VII gene involved in the biosynthesis of the leukocyte sialyl Lewis X, which may be related to tissue infiltration in patients with malignant adult T-cell leukemia. HTLV-1 induces Fuc-T VII transcription through the viral transactivator Tax, although the underlying molecular mechanism remains unknown. In the present study, we analyzed the role of the cis-activating element in Tax activation using reporter constructs bearing the 5'-regulatory region of Fuc-T VII in Jurkat T cells. A sequence (GGCTGTGGGGGCGTCATATTGCCCTGG) covering a half-palindromic cyclic adenosine monophosphate (cAMP)-responsive element (CRE) was found to be required for Tax activation of the Fuc-T VII promoter. We further demonstrated that transcription factors of the CRE-binding protein (CREB)/activating transcription factor (ATF) family bind to this CRE-like sequence and that Tax binds in association with CREB and the coactivator CREB-binding protein (CBP) in Jurkat T cells. This element, containing the G+C-rich flanking sequences, is homologous to the Tax-responsive viral CREs in the HTLV-1 long terminal repeat (LTR)-promoter. Furthermore, CREM alpha, an isoform of CREB deficient in the glutamine-rich domains, was found to activate the Fuc-T VII promoter in a phosphorylation-independent manner, similar to the viral CRE in HTLV-1 LTR but in contrast to the phosphorylation-dependent activation of the cellular CREs by Tax. These findings indicate that the Fuc-T VII promoter is transactivated by Tax in concert with CBP through a CRE-like sequence in a manner similar to that of viral CRE in HTLV-1 LTR.
Hiraiwa
Nozomu
N
Division of Molecular Pathology, Aichi Cancer Center, Chikusa-ku, Nagoya, Japan.
Yabuta
Tomonori
T
Yoritomi
Keijiro
K
Hiraiwa
Miki
M
Tanaka
Yuetsu
Y
Suzuki
Takeshi
T
Yoshida
Mitsuaki
M
Kannagi
Reiji
R
D020121:5' Untranslated Regions / Q000235:genetics*; D051698:Activating Transcription Factor 2; D000242:Cyclic AMP / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005647:Fucosyltransferases / Q000096:biosynthesis / Q000235:genetics*; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000502:physiology*; D016355:Genes, pX; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells / Q000201:enzymology / Q000821:virology; D008957:Models, Genetic; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000235:genetics*; D015290:Second Messenger Systems / Q000502:physiology*; D012689:Sequence Homology, Nucleic Acid; D013329:Structure-Activity Relationship; D020079:Terminal Repeat Sequences; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation
D020121:5' Untranslated Regions; D051698:Activating Transcription Factor 2; D017362:Cyclic AMP Response Element-Binding Protein; D016356:Gene Products, tax; D014157:Transcription Factors; D000242:Cyclic AMP; D005647:Fucosyltransferases; C031692:galactoside 3-fucosyltransferase