Constitutive phosphorylation and turnover of I kappa B alpha in human T-cell leukemia virus type I-infected and Tax-expressing T cells.
Human T-cell leukemia virus type I (HTLV-I) encodes a strong transcriptional activator, Tax, that stimulates transcription indirectly through the viral long terminal repeat and also activates a number of cellular genes via association with host transcription factors. The NF-kappa B/Rel pathway is a target for Tax trans-activation, and Tax has been correlated with increased NF-kappa B-binding activity and NF-kappa B-dependent gene expression in HTLV-I-infected cells. In this study we demonstrate that constitutive phosphorylation and increased turnover of the regulatory I kappa B alpha protein in HTLV-I-infected MT-2 and C8166 cells and Tax-expressing 19D cells contribute to constitutive NF-kappa B-binding activity, which consists primarily of c-Rel, p52(NFKB2), and p50(NFKB1). I kappa B alpha mRNA expression is also increased 7- to 20-fold in these cells, although the steady-state level of I kappa B alpha protein is reduced in HTLV-I-infected and Tax-expressing T cells. These results indicate that the viral Tax protein, by indirectly mediating phosphorylation of I kappa B, may target I kappa B alpha for rapid degradation, thus leading to constitutive NF-kappa B activity.
Lacoste
J
J
Abe Stern Cancer Research Laboratory, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Montréal, Québec, Canada.
Petropoulos
L
L
Pépin
N
N
Hiscott
J
J
D001483:Base Sequence; D016356:Gene Products, tax / Q000096:biosynthesis*; D015368:Human T-lymphotropic virus 1; D006801:Humans; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009838:Oligodeoxyribonucleotides; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism* / Q000821:virology; D051841:Transcription Factor RelB; D014157:Transcription Factors
D016356:Gene Products, tax; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D011518:Proto-Oncogene Proteins; C497593:RELB protein, human; D012333:RNA, Messenger; D014157:Transcription Factors; D051841:Transcription Factor RelB