95021266.1 Human T-cell leukemia virus type I Tax activation of NF-kappa B/Rel involves phosphorylation and degradation of I kappa B alpha and RelA ( p65 ) -mediated induction of the c-rel gene . (ncsubj involves:12 activation:8 _) (ncmod _ activation:8 Tax:7) (ncmod _ Tax:7 T-cell_leukemia_virus_type_I:2:6) (ncmod _ T-cell_leukemia_virus_type_I:2:6 Human:1) (dobj involves:12 and:14) (conj and:14 phosphorylation:13) (conj and:14 degradation:15) (iobj activation:8 of:9) (dobj of:9 NF-kappa_B/Rel:10:11) (iobj and:14 of:16) (dobj of:16 induction:27) (ta bal RelA:22 p65:24) (conj and:21 RelA:22) (conj and:21 I_kappa_B_alpha:17:20) (ncmod _ and:21 -mediated:26) (ncmod _ induction:27 and:21) (iobj induction:27 of:28) (dobj of:28 c-rel_gene:30:31) (det c-rel_gene:30:31 the:29) 95021266.2 The tax gene product of human T-cell leukemia virus type I ( HTLV-I ) is a potent transcriptional activator that both stimulates viral gene expression and activates an array of cellular genes involved in T-cell growth . (det tax_gene_product:2:4 The:1) (iobj tax_gene_product:2:4 of:5) (dobj of:5 human_T-cell_leukemia_virus_type_I:6:11) (ta bal human_T-cell_leukemia_virus_type_I:6:11 HTLV-I:13) (ncsubj is:15 tax_gene_product:2:4 _) (xcomp _ is:15 transcriptional_activator:18:19) (det transcriptional_activator:18:19 a:16) (ncmod _ transcriptional_activator:18:19 potent:17) (cmod that:20 transcriptional_activator:18:19 and:26) (conj and:26 stimulates:22) (conj and:26 activates:27) (dobj expression:25 stimulates:22) (ncmod _ expression:25 viral_gene:23:24) (dobj activates:27 array:29) (det array:29 an:28) (iobj array:29: of:30) (dobj of:30 cellular_genes:31:32) (ncsubj involved:33 cellular_genes:31:32 _) (xmod cellular_genes:31:32 involved:33) (iobj involved:33 in:34) (dobj in:34 T-cell_growth:35:36) 95021266.3 Tax acts indirectly by inducing or modifying the action of various host transcription factors , including members of the NF-kappa B/Rel family of enhancer-binding proteins . (ncsubj acts:2 Tax:1 _) (xmod _ acts:2 by:4) (ncmod _ by:4 indirectly:3) (conj or:6 inducing:5) (conj or:6 modifying:7) (dobj or:6 action:9) (det action:9 the:8) (iobj action:9 of:10) (dobj of:10 transcription_factors:13:14) (ncmod _ transcription_factors:13:14 host:12) (ncmod _ transcription_factors:13:14 various:11) (xmod _ transcription_factors:13:14 including:16) (dobj including:16 members:17) (iobj members:17 of:18) (dobj of:18 NF-kappa_B/Rel_family:20:22) (det NF-kappa_B/Rel_family:20:22 the:19) (iobj NF-kappa_B/Rel_family:20:22 of:23) (dobj of:23 enhancer-binding_proteins:24:25) 95021266.4 In resting T cells , many of these NF-kappa B/Rel factors are sequestered in the cytoplasm by various ankyrin-rich inhibitory proteins , including I kappa B alpha . (xmod _ sequestered:13 In:1) (dobj In:1 resting_T_cells:2:4) (ncsubj sequestered:13 many:6 obj) (passive sequestered:13) (aux sequestered:13 are:12) (ncmod _ many:6 of:7) (det NF-kappa_B/Rel_factors:9:11 these:8) (dobj of:7 NF-kappa_B/Rel_factors:9:11) (iobj sequestered:13 in:14) (dobj in:14 cytoplasm:16) (det cytoplasm:16 the:15) (ncmod _ cytoplasm:16 by:17) (dobj by:17 ankyrin-rich_inhibitory_proteins:19:21) (ncmod _ ankyrin-rich_inhibitory_proteins:19:21 various:18) (xmod _ ankyrin-rich_inhibitory_proteins:19:21 including:23) (dobj including:23 ankyrin-rich_inhibitory_proteins:19:21) 95021266.5 HTLV-I Tax expression leads to the constitutive nuclear expression of biologically active NF-kappa B and c-Rel complexes ; however , the biochemical mechanism ( s ) underlying this response remains poorly understood . (conj ;:18 remains:30) (conj ;:18 leads:4) (ncsubj leads:4 HTLV-I_Tax_expression:1:3 _) (iobj leads:4 to:5) (dobj to:5 constitutive_nuclear_expression:7:9) (det constitutive_nuclear_expression:7:9 the:6) (iobj constitutive_nuclear_expression:7:9 of:10) (dobj of:10 and:15) (conj and:15 NF-kappa_B:13:14) (conj and:15 c-Rel_complexes:16:17) (ncmod _ and:15 active:12) (ncmod _ active:12 biologically:11) (ncmod _ remains:30 however:19) (ncsubj remains:30 mechanism:23 _) (passive understood:32) (xcomp _ remains:30 understood:32) (ncmod _ understood:32 poorly:31) (det biochemical_mechanism:22:23 the:21) (ta bal biochemical_mechanism:22:23 s:25) (ncsubj underlying:27 biochemical_mechanism:22:23 _) (xmod _ biochemical_mechanism:22:23 underlying:27) (dobj underlying:27 response:29) (det response:29 this:28) 95021266.6 In this study , we demonstrate that Tax-stimulated nuclear expression of NF-kappa B in both HTLV-I-infected and Tax-transfected human T cells is associated with the phosphorylation and rapid proteolytic degradation of I kappa B alpha . (ncmod _ demonstrate:6 In:1) (dobj In:1 study:3) (det study:3 this:2) (ncsubj demonstrate:6 we:5 _) (ccomp that:7 demonstrate:6 associated:23) (ncsubj associated:23 Tax-stimulated_nuclear_expression:8:10 obj) (aux associated:23 is:22) (passive associated:23) (iobj associated:23 with:24) (dobj with:24 and:27) (det and:27 the:25) (conj and:27 phosphorylation:26) (conj and:27 proteolytic_degradation:29:30) (ncmod _ proteolytic_degradation:29:30 rapid:28) (iobj and:27 of:31) (dobj of:31 I_kappa_B_alpha:32:35) (iobj Tax-stimulated_nuclear_expression:8:10 of:11) (dobj of:11 NF-kappa_B:12:13) (iobj NF-kappa_B:12:13 in:14) (conj and:17 Tax-transfected:18) (conj and:17 HTLV-I-infected:16) (ncmod _ human_T_cells:19:21 Tax-transfected:18) (ncmod _ human_T_cells:19:21 HTLV-I-infected:16) 95021266.7 In contrast to prior in vitro studies , at least a fraction of the phosphorylated form of I kappa B alpha remains physically associated with the NF-kappa B complex in vivo but is subject to rapid degradation , thereby promoting the nuclear translocation of the active NF-kappa B complex . (ncmod _ contrast:2 prior:4) (dobj in:5 vitro:6) (ncmod _ studies:7 in:5) (dobj In:1 contrast:2) (ncmod _ contrast:2 to:3) (dobj to:3 studies:7) (ncmod _ remains:22 In:1) (dobj at:9 least:10) (ncmod _ remains:22 at:9) (det fraction:12 a:11) (iobj fraction:12 of:13) (dobj of:13 form:16) (det form:16 the:14) (passive phosphorylated:15) (ncsubj phosphorylated:15 form:16 obj) (ncmod _ form:16 phosphorylated:15) (iobj form:16 of:17) (dobj of:17 I_kappa_B_alpha:18:21) (xcomp _ remains:22 but:32) (conj but:32 associated:24) (conj but:32 is:33) (ncsubj remains:22 fraction:12 _) (ncmod _ associated:24 physically:23) (iobj associated:24 with:25) (dobj with:25 NF-kappa_B_complex:27:29) (ncmod _ NF-kappa_B_complex:27:29 in:30) (dobj in:30 vivo:31) (det NF-kappa_B_complex:27:29 the:26) (passive associated:24) (xcomp _ is:33 subject:34) (ncmod _ subject:34 to:35) (dobj to:35 degradation:37) (ncmod _ degradation:37 rapid:36) (xmod _ fraction:12 promoting:40) (ncmod _ promoting:40 thereby:39) (dobj promoting:40 translocation:43) (det translocation:43 the:41) (ncmod _ translocation:43 nuclear:42) (iobj translocation:43 of:44) (dobj of:44 NF-kappa_B_complex:47:49) (det NF-kappa_B_complex:47:49 the:45) (ncmod _ NF-kappa_B_complex:47:49 active:46) 95021266.8 We further demonstrate that Tax induction of nuclear c-Rel expression is activated by the RelA ( p65 ) subunit of NF-kappa B , which activates transcription of the c-rel gene through an intrinsic kappa B enhancer element . (ncsubj demonstrate:3 We:1 _) (ncmod _ demonstrate:3 further:2) (ccomp that:4 demonstrate:3 activated:12) (ncsubj activated:12 Tax_induction:5:6 obj) (aux activated:12 is:11) (passive activated:12) (iobj activated:12 by:13) (cmod _ subunit:19 activates:25) (ncsubj activates:25 which:24 _) (dobj activates:25 transcription:26) (iobj transcription:26 of:27) (dobj of:27 c-rel_gene:29:30) (det c-rel_gene:29:30 the:28) (ncmod _ c-rel_gene:29:30 through:31) (dobj through:31 element:37) (det kappa_B_enhancer_element:34:37 an:32) (ncmod _ kappa_B_enhancer_element:34:37 intrinsic:33) (dobj by:13 subunit:19) (det subunit:19 the:14) (ncmod _ subunit:19 RelA:15) (ta brack subunit:19 p65:17) (iobj subunit:19 of:20) (dobj of:20 NF-kappa_B:21:22) (iobj Tax_induction:5:6 of:7) (dobj of:7 nuclear_c-Rel_expression:8:10) 95021266.9 In normal cells , the subsequent accumulation of nuclear c-Rel acts to inhibit its own continued production , indicating the presence of an autoregulatory loop . (det accumulation:7 the:5) (ncmod _ accumulation:7 subsequent:6) (iobj accumulation:7 of:8) (dobj of:8 nuclear_c-Rel:9:10) (dobj In:1 cells:3) (ncmod _ cells:3 normal:2) (ncmod _ acts:11 In:1) (xmod _ acts:11 indicating:19) (dobj indicating:19 presence:21) (det presence:21 the:20) (iobj presence:21 of:22) (dobj of:22 autoregulatory_loop:24:25) (det autoregulatory_loop:24:25 an:23) (ncsubj acts:11 accumulation:7 _) (xcomp to acts:11 inhibit:13) (ccomp _ inhibit:13 continued:16) (ncsubj continued:16 own:15 _) (dobj continued:16 production:17) (det own:15 its:14)