Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20226 (TATA-binding protein)
 1,297 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transcription of the E1A gene of the highly oncogenic adenovirus 12 (Ad12) initiates at two start sites (TS1 and TS2). We have previously shown that the E2F and ATF motifs distal of TS1 co-operatively participate in E1A autostimulation from the TS1 promoter region. Here we report the identification of a second E2F-like target region (E2DFII) immediately upstream of the E1A-stimulating factor 1 binding site (ESF-1), important for 13S-mediated autoactivation from TS2. Reporter constructs lacking distinct TS2 cis-acting elements were analysed for their levels of CAT expression in the absence and presence of the E1A 13S protein in transient expression assays. In the absence of 13S, full promoter activity was observed only for a construct containing all elements (the E2F-like motif, and E-Box and the TATA element). Promoter activation increased significantly in Ad12 E1A-co-transfected cells. Induction by the 13S protein was also detected for the construct containing a non-functional ESF-1 sequence. Our results indicate that the E2F-like motif is responsible for activation medicated by the 13S protein from TS2, while ESF-1-or TATA-binding protein activity were not involved. Additionally, the TATA sequence appeared to be dispensable for transactivation. Gel-shift experiments using the E2F-like promoter element as a probe indicated the binding of an E2F-5 or E2F-5-like transcription factor to this region. We conclude that transcription through the TS1 as well as the TS2 promoter region is stimulated by the Ad 12 13S protein. Moreover, transfection of the construct including both TS1 and TS2 indicates an E2F-site-mediated synergism between both regions with respect ot E1A-induced transactivation.
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PMID:A cis-acting element 7 bp upstream of the ESF-1-binding motif is involved in E1A 13S autoregulation of the adenovirus 12 TS2 promoter. 912 62

Human T-cell leukemia virus type-I (HTLV-I), the etiologic agent of adult T-cell leukemia (ATL) transforms human T cells both in vivo and in vitro. However, the long latency period between infection and development of ATL, as well as the small fraction of the infected population that actually develops this disease, suggest that factors in addition to the virus are involved in its pathogenesis. Mutation of tumor suppressor gene p53 has been found in both HTLV-I-transformed T-cell lines and ATL cases at relatively low frequency. However, increasing evidence supports p53 functional impairment in HTLV-I-transformed T cells. Tax, the major transactivator of HTLV-I, is critical for the initial events involved in transformation. We have considered the possibility that p53 may regulate transcription of viral and cellular genes important for viral replication and transformation. Inactivation of p53 function might then permit constitutive expression of these viral and cellular genes. We have investigated the effects of wild-type and mutant p53 on Tax-mediated activation of the HTLV-I long terminal repeat (LTR) and the promoters of several cellular genes including the interleukin (IL)-1alpha, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF ), and IL-2 receptor alpha chain gene. Jurkat, HuT78, and U937 cells were cotransfected with plasmids containing a chloramphenicol acetyltransferase (CAT ) reporter gene under viral or cellular promoter control and the Tax expression vector, in addition to vectors for a wild-type or mutant p53. Wild-type p53 is a potent repressor of viral and cellular activation by Tax. Mutations within p53 severely inhibit this downregulation. We also show that wild-type p53 suppresses transcription from the HTLV-I LTR in Jurkat-Tax, a T-cell line stably expressing Tax, and MT-2, a HTLV-I-transformed T-cell line. Wild-type, but not mutant, p53 interfered with the binding of TATA-binding protein (TBP) to the TATA motif of the HTLV-I LTR. These results suggest that p53 inactivation may lead to upregulation of viral and cellular genes and may also be important for establishment of productive viral infection and development of ATL.
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PMID:Repression of transcription from the human T-cell leukemia virus type I long terminal repeat and cellular gene promoters by wild-type p53. 938 10

Varicella-zoster virus open reading frame 4-encoded protein (IE4) possesses transactivating properties for varicella-zoster virus genes as well as for those of heterologous viruses such as the human immunodeficiency virus type 1 (HIV-1). Mechanisms of HIV-1 LTR (long terminal repeat) transactivation were investigated in HeLa cells transiently transfected with an IE4 expression plasmid and a CAT reporter gene under the control of the HIV-1 LTR. These results demonstrated that IE4-mediated transactivation of the HIV-1 LTR in HeLa cells required transcription factor kappaB (NF-kappaB). Using the gel retardation assay, it was shown that transfection of the IE4 expression vector in HeLa cells was not associated with induction of NF-kappaB under the p50.p65 heterodimeric form and that no direct binding of IE4 to the kappaB sites could be detected. Both Western blot and immunofluorescence analyses suggested that the ability of IE4 to activate transcription through kappaB motives was not connected with its capacity to override the inhibitory activities of IkappaB-alpha or p105. Finally, in vitro protein-protein interactions involving IE4 and basal transcription factors such as TATA-binding protein and transcription factor IIB were carried out. A direct interaction between IE4 and TATA-binding protein or transcription factor IIB components of the basal complex of transcription was evidenced, as well as binding to the p50 and p65 NF-kappaB subunits. Mutagenesis analysis of IE4 indicated that the COOH-terminal cysteine-rich and arginine-rich regions (residues 82-182) were critical for transactivation, whereas the first 81 amino acids appeared dispensable. Moreover, the arginine-rich region is required for the in vitro binding activity, whereas the COOH-terminal end did not appear essential.
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PMID:Activation of the human immunodeficiency virus long terminal repeat by varicella-zoster virus IE4 protein requires nuclear factor-kappaB and involves both the amino-terminal and the carboxyl-terminal cysteine-rich region. 959 2