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)

RB, the protein product of the retinoblastoma tumor-suppressor gene, regulates the activity of specific transcription factors. This regulation appears to be mediated either directly through interactions with specific transcription factors or through an alternative mechanism. Here we report that stimulation of Sp1-mediated transcription by RB is partially abrogated at the nonpermissive temperature in ts13 cells. These cells contain a temperature-sensitive mutation in the TATA-binding protein-associated factor TAFII250, first identified as the cell cycle regulatory protein CCG1. The stimulation of Sp1-mediated transcription by RB in ts13 cells at the nonpermissive temperature could be restored by the introduction of wild-type human TAFII250. Furthermore, we demonstrate that RB binds directly to hTAFII250 in vitro and in vivo. These results suggest that RB can confer transcriptional regulation and possibly cell cycle control and tumor suppression through an interaction with TFIID, in particular with TAFII250.
 ...
PMID:The retinoblastoma-susceptibility gene product binds directly to the human TATA-binding protein-associated factor TAFII250. 772 24

The growth suppressor activities of the RB and p107 products are believed to be mediated by the reversible binding of a heterogeneous family of cellular proteins to a conserved T/E1A pocket domain that is present within both proteins. To study the functional role of these interactions, we examined the properties of cellular retinoblastoma binding protein 2 (RBP2) binding to RB, p107, and the related TATA-binding protein (TBP) product. We observed that although RBP2 bound exclusively to the T/E1A pocket of p107, it could interact with RB through independent T/E1A and non-T/E1A domains and with TBP only through the non-T/E1A domain. Consistent with this observation, we found that a mutation within the Leu-X-Cys-X-Glu motif of RBP2 resulted in loss of ability to precipitate p107, while RB- and TBP-binding activities were retained. We located the non-T/E1A binding site of RBP2 on a 15-kDa fragment that is independent from the Leu-X-Cys-X-Glu motif and encodes binding activity for RB and TBP but does not interact with p107. Despite the presence of a non-T/E1A binding site, however, recombinant RBP2 retained the ability to preferentially precipitate active hypophosphorylated RB from whole-cell lysates. In addition, we found that cotransfection of RBP2 can reverse in vivo RB-mediated suppression of E2F activity. These findings confirm the differential binding specificities of the related RB, p107, and TBP proteins and support the presence of multifunctional domains on the nuclear RBP2 product which may allow complex interactions with the cellular transcription machinery.
 ...
PMID:Differential specificity for binding of retinoblastoma binding protein 2 to RB, p107, and TATA-binding protein. 793 40

The retinoblastoma tumor suppressor gene product (Rb) binds directly to the largest TFIID subunit, TATA-binding protein associated factor TAF(II)250, first identified as the cell cycle regulatory protein CCG1. Here we map the domains in Rb and TAF(II)250 important for their interaction in vitro and in vivo. Both the amino terminus and the large pocket of Rb are able to associate independently with TAF(II)250. The binding domain(s) within the large pocket are distinct from the viral oncoprotein and E2F binding region since certain pocket mutations, which abolish E1A binding, do not abolish TAF(II)250 binding. Consistent with the large pocket of Rb binding to TAF(II)250, the large pocket domains of both p107 and p130 are able to bind to TAF(II)250 in vivo. We also demonstrate that at least two regions of TAF(II)250 are able to bind to the large pocket of Rb independently whereas the amino terminus of Rb binds to a distinct domain in TAF(II)250. We further demonstrate that Rb can bind to TFIID in vitro, presumably in part through an interaction with TAF(II)250. Our results suggest a complex interaction between Rb and TAF(II)250 and imply that TAF(II)250, TFIID, and potentially other basal transcription factors are targets for regulation by Rb and Rb-related proteins.
 ...
PMID:Rb interacts with TAF(II)250/TFIID through multiple domains. 924 74

The transcriptional activator E2F1 regulates the expression of genes at the G1/S boundary. We have characterized interactions of the E2F1 activation domain with two general transcription factors, the TATA-box binding protein (TBP) and TFIIH. Two distinct binding sites on E2F1 were identified for TBP (amino acids 386-417 and 415-437) each of which supported activation in mammalian cells when expressed as a fusion to a heterologous DNA-binding domain. Neither of these minimal activation domains independently bound TFIIH; rather, the TFIIH binding site of E2F1 overlaps both domains. Loss of TFIIH-binding by E2F1 resulted in a 60-65% reduction in transactivation, suggesting that the E2F1/TFIIH interaction is important, but not essential, for transactivation. The retinoblastoma protein (Rb) binds directly to E2F1 and represses E2F1-mediated transactivation. We have demonstrated that recombinant Rb can compete with TBP and the p62 subunit of TFIIH for binding to immobilized E2F1. A tumorigenic form of Rb deficient in repressing E2F1-mediated transactivation is likewise deficient in displacing TBP from E2F1. We propose that competition between Rb and both TBP and TFIIH for binding to E2F1 is a mechanism by which Rb inhibits transactivation by E2F1.
 ...
PMID:Modular organization of the E2F1 activation domain and its interaction with general transcription factors TBP and TFIIH. 940 Sep 91

The retinoblastoma (RB) tumour suppressor protein negatively regulates cell proliferation by modulating transcription of growth-regulatory genes. Recruitment of Rb to promoters, by association with E2F complex or by fusion with heterologous DNA-binding domains, demonstrated that Rb represses directly transcription. Recent studies also suggest that the RB protein is able to repress gene transcription mediated by the RNA polymerase I and III. Since the TATA-binding protein (TBP) is an important component for transcription mediated by all three RNA polymerases, we have analysed the functional interaction between Rb and TBP in vivo in the context of RNA pol II-driven transcription. We demonstrated that in mammalian cells Rb tethered to promoter represses TBP-mediated activation in vivo, and Rb-mediated repression is reversed in the presence of the inhibition of histone deacetylase activity by trichostatin A (TSA).
 ...
PMID:Retinoblastoma protein tethered to promoter DNA represses TBP-mediated transcription. 967 Dec 33

The retinoblastoma tumor suppressor protein, Rb, interacts directly with the largest TATA-binding protein-associated factor, TAFII250, through multiple regions in each protein. To define the potential role(s) of this interaction, we examined whether Rb could regulate the intrinsic, bipartite kinase activity of TAFII250. Here, we report that Rb is able to inhibit the kinase activity of immunopurified and gel-purified recombinant TAFII250. Rb inhibits the autophosphorylation of TAFII250 as well as its phosphorylation of the RAP74 subunit of TFIIF in a dose-responsive manner. Inhibition of TAFII250 kinase activity involves the Rb pocket (amino acids 379 to 928) but not its amino terminus. In addition, Rb appears to specifically inhibit the amino-terminal kinase domain of TAFII250 through a direct protein-protein interaction. We further demonstrate that two different tumor-derived Rb pocket mutants, C706F and Deltaex22, are functionally defective for kinase inhibition, even though they are able to bind the amino terminus of TAFII250. Our results suggest a novel mechanism of transcriptional regulation by Rb, involving direct interaction with TAFII250 and inhibition of its ability to phosphorylate itself, RAP74, and possibly other targets.
 ...
PMID:Rb inhibits the intrinsic kinase activity of TATA-binding protein-associated factor TAFII250. 985 7

Pax-5 codes for the transcription factor BSAP, which plays an important role in midbrain patterning, B cell development, and lymphoma formation. Pax-5 is known to control gene expression by recognizing its target genes via the NH2-terminal paired domain and by regulating transcription through a COOH-terminal regulatory module consisting of activating and inhibitory sequences. The central region of Pax-5 contains a sequence with significant homology to the first alpha-helix of the paired-type homeodomain. This partial homeodomain has been highly conserved throughout vertebrate evolution because it is found not only in Pax-5 but also in the related Pax-2 and Pax-8 members of the same Pax subfamily. Here we report that the partial homeodomain binds the TATA-binding protein (TBP) and retinoblastoma (Rb) gene product. Both TBP and Rb were shown by coimmunoprecipitation experiments to directly associate with Pax-5 in vivo. The conserved core domain of TBP and the pocket region as well as COOH-terminal sequences of Rb are required for interaction with the partial homeodomain of Pax-5 in in vitro binding assays. Furthermore, Pax-5 was specifically bound only by the underphosphorylated form of Rb. These data indicate that Pax-5 is able to contact the basal transcription machinery through the TBP-containing initiation factor TFIID, and that its activity can be controlled by the cell cycle-regulated association with Rb.
 ...
PMID:The partial homeodomain of the transcription factor Pax-5 (BSAP) is an interaction motif for the retinoblastoma and TATA-binding proteins. 1019 86

Circulating platelets, essential for thrombosis and hemostasis, originate from megakaryocytes. Megakaryocyte growth, differentiation and survival processes are regulated by the c-Mpl receptor ligand. In the current study we used differential display to identify part of the program of genes regulated during Mpl ligand-induced murine megakaryocyte differentiation. Several of the genes, including the retinoblastoma binding protein p84, were found to be induced, while others were repressed. One such repressed gene was identified as a TATA-binding protein (TBP)-Associated Factor (TAF) family member, TAF(II)32, previously reported to be upregulated during apoptosis. Our analysis of various cell types suggested that the previously identified species homologs, human TAF(II)32 and murine TAF(II)32, are in fact different isoforms, which we propose to re-name TAF(II)32alpha and TAF(II)32beta, respectively. Only the TAF(II)32beta isoform is regulated during Mpl ligand-induced megakaryocyte differentiation, which suggests individual roles for the two forms.
 ...
PMID:Repression of A TAF(II)32 isoform as part of a program of genes regulated during mpl ligand-induced megakaryocyte differentiation. 1044 67

The two alleles of the 30 kDa TATA-binding protein associated factor (TAF(II)30) gene, have been targeted by homologous recombination in murine F9 embryonal carcinoma cells and subsequently disrupted using a Cre recombinase-loxP strategy. The TAF(II)30-null cells are not viable, but are rescued by the expression of human TAF(II)30. Cells lacking TAF(II)30 are blocked in G(1)/G(0) phase of the cell cycle and undergo apoptosis. In agreement with the G(1) arrest phenotype, the expression of cyclin E is impaired and the retinoblastoma protein is hypophosphorylated in the TAF(II)30-null cells. Interestingly, retinoic acid (RA) treatment prevented TAF(II)30-null cell death and induced primitive endodermal differentiation. In contrast, the RA- and cAMP-induced parietal endodermal differentiation was impaired in the TAF(II)30-null cells. Thus, TAF(II)30 is not indispensable for class II gene transcription in general, but seems to be required for the expression of a subset of genes.
 ...
PMID:Mammalian TAF(II)30 is required for cell cycle progression and specific cellular differentiation programmes. 1046 60

Using RNA arbitrarily primed PCR, the authors selected for transcripts with cell cycle-related differential expression in cultured human melanocytes. Among the partial cDNAs cloned, a novel cDNA was identified, which showed 54% identity to the recently cloned cDNA of the retinoblastoma binding protein-2 (RBP2). The 6.5-kB full-length cDNA of this RBP2-related gene, termed RBP2 homolog 1 (RBP2-H1), was obtained from a human teratocarcinoma cDNA library. Two independent libraries from human malignant melanomas were negative. A computerized sequence analysis revealed highly conserved motifs with possible functional meaning: two domains that, in the RBP2 homolog, mediate the binding and interaction with the proteins encoded by the retinoblastoma susceptibility gene, the TATA-binding protein, and the oncoprotein rhombotin 2; in addition, two DNA-binding zinc finger/leukemia-associated protein motifs were detected. Because a functional role in cell-cycle control and transcriptional activation can be envisioned, we investigated the expression of this novel transcript in normal fetal and adult tissues, as well as tissues of benign and malignant melanocytic tumors. By conducting multiple Northern blot, RT-PCR, and in situ hybridization analyses, the authors showed that the corresponding mRNA is expressed in virtually all normal tissues. Accordingly, they found RBP2-H1 expression in microdissected tissue samples from benign melanocytic nevi (n = 10). In contrast, the transcript is significantly down-regulated or even lost in tissue samples from human malignant melanomas (n = 13), melanoma metastases (n = 10), and melanoma cell lines (n = 7). The authors concluded that the loss or down-regulation of RBP2-H1 expression could be a useful molecular marker for a transformed phenotype in the human melanocytic system.
 ...
PMID:Deficiency of a novel retinoblastoma binding protein 2-homolog is a consistent feature of sporadic human melanoma skin cancer. 1061 11


1 2 Next >>