Human TAFII30 is present in a distinct TFIID complex and is required for transcriptional activation by the estrogen receptor

Jacq, Xavier; Brou, Christel; Lutz, Yves; Davidson, Irwin; Chambon, Pierre; Tora, Làszlò

doi:10.1016/0092-8674(94)90404-9

Cited by 382 publications

(329 citation statements)

References 44 publications

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“…Since this breast cancer cDNA encoded a nuclear receptor-binding auxiliary protein (Segars et al, 1993), we called the gene brx. Overlapping cDNA clones were consistent with a 5.3 kilobase cDNA encoding a 1428 amino acid protein with a 168 kilodalton predicted molecular mass distinct from proteins reported to bind nuclear hormone receptors (Cavailles et al, 1994(Cavailles et al, , 1995Halachmi et al, 1994;Jacq et al, 1994;Chen and Evans, 1995;Horlein et al, 1995;Onate et al, 1995;Le Douarin et al, 1995;Baniahmad et al, 1995).…”

Section: Identi®cation and Cloning Of Brx Cdnasupporting

confidence: 55%

“…In addition, ligand was not required for in vitro binding of Brx to ER, and in fact the addition of estrogen (Figure 4e) and tamoxifen (not shown) only slightly augmented binding. A non-ligand dependent interaction has been noted for some NHR-binding proteins (Jacq et al, 1994), and in some in vitro studies (Cavailles et al, 1995). Two observations suggest that the mechanism by which Brx functions may involve association with unliganded ER in the cell.…”

Section: Discussionmentioning

confidence: 90%

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Characterization of Brx, a novel Dbl family member that modulates estrogen receptor action

et al. 1998

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Regulation of gene activation by the estrogen receptor (ER) is complex and involves co-regulatory proteins, oncoproteins (such as Fos and Jun), and phosphorylation signaling pathways. Here we report the cloning and initial characterization of a novel protein, Brx, that contains a region of identity to the oncogenic Rhoguanine nucleotide exchange (Rho-GEF) protein Lbc, and a unique region capable of binding to nuclear hormone receptors, including the ER. Western and immunohistochemistry studies showed Brx to be expressed in estrogen-responsive reproductive tissues, including breast ductal epithelium. Brx bound speci®cally to the ER via an interaction that required distinct regions of ER and Brx. Furthermore, overexpression of Brx in transfection experiments using an estrogenresponsive reporter revealed that Brx augmented gene activation by the ER in an element-speci®c and liganddependent manner. Moreover, activation of ER by Brx could be speci®cally inhibited by a dominant-negative mutant of Cdc42Hs, but not by dominant negative mutants of RhoA or Rac1. Taken together, these data suggest that Brx represents a novel modular protein that may integrate cytoplasmic signaling pathways involving Rho family GTPases and nuclear hormone receptors.

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Section: Identi®cation and Cloning Of Brx Cdnasupporting

confidence: 55%

Section: Discussionmentioning

confidence: 90%

Characterization of Brx, a novel Dbl family member that modulates estrogen receptor action

et al. 1998

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“…Their synthesis would represent another mechanism for modifying TFIID structure and function, besides post-translation modi®cations of TBP and TAF II s (Boyer and Berk, 1993;Segil et al, 1996) and the selective addition of cell-and promoter-speci®c subunits (Jacq et al, 1994;Bertolotti et al, 1996;Dikstein et al, 1996). Less likely, they could be mRNA molecules with a di erent primary structure but sharing a common motif, as hypothesized for the various transcripts detected by the 5' segment of TBP cDNA (Purrello et al, 1994a, and unpublished results).…”

Section: Northern Analysis Of Taf II Transcriptsmentioning

confidence: 99%

Genomics and transcription analysis of human TFIID

et al. 1998

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TFIID, a multisubunit protein comprised of TBP (TATA box-binding protein) and TAF II s (TBP-associated factors), has a central role in transcription initiation at class II promoters. TAF II s role as mediators of regulatory transcription factors, such as pRb and p53, and their involvement in signal transduction pathways suggest that some may participate in the control of cell proliferation and di erentiation: therefore, they could be considered potential protooncogenes or antioncogenes. With the aim of starting to analyse these potential roles, we have determined the genomic position of nine human TAF II genes (TAF II 250, TAF II 135, TAF II 100, TAF II 80, TAF II 55, TAF II 43, TAF II 31, TAF II 28, TAF II 20/15) and of two previously unknown sequences related to TAF II 250 and TAF II 31, respectively. Except for those encoding TAF II 250 and TAF II 31, these genes are present in a single copy and, with the exclusion of those for TAF II 43 and TAF II 28 (both at 6p21), are localized in di erent segments of the genome. Indeed, six of them map to a chromosomal region commonly altered in speci®c neoplasias, which de®nes them as candidates for involvement in oncogenesis. Our experiments also demonstrate that TAF II transcripts are synthesized ubiquitously, mostly at low levels similar to those of TBP. Interestingly, the amount of the major mRNA species detected by TAF II 20/15 cDNA is higher, which suggests that the polypeptide it encodes may also perform functions independently of TFIID. TAF II isoforms, indicated by additional bands on Northern blots, may play a role in modulation of TFIID function. These data will be useful for analysing variations of TAF II mRNA phenotype during cell proliferation, di erentiation and development, both normal and pathological.

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confidence: 99%

“…Not only are TAF II s components of transcription factor TFIID, but distinct subsets of TAF II s are also components of the SAGA, PCAF, and TFTC complexes (13,14,21,31,40). For human TFIID (hTFIID), cDNAs for 11 hTAF II s have been characterized (10,16,18,24,25).Genetic and biochemical experiments show that some TAF II s are important for promoter recognition and expression of a subset of promoters (15,38,39), while others are more generally required for transcription in Saccharomyces cerevisiae (2,26,27,29 Expression of hTAF II 28 also potentiates ligand-dependent activation by the AF-2s of many NRs, the most dramatic effects being seen with the receptors for 9-cis retinoic acid (retinoid X receptor), estrogen (estrogen receptor [ER]), and the VDR (22). Deletion analysis showed that coactivator activity required amino acids 150 to 179 in the C-terminal domain of hTAF II 28.…”

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confidence: 99%

Synergistic Transcriptional Activation by TATA-Binding Protein and hTAF_II28 Requires Specific Amino Acids of the hTAF_II28 Histone Fold

Lavigne

Gangloff

et al. 1999

Molecular and Cellular Biology

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Coexpression of the human TATA-binding protein (TBP)-associated factor 28 (hTAF II 28) with the alteredspecificity mutant TBP spm3 synergistically enhances transcriptional activation by the activation function 2 of the nuclear receptors (NRs) for estrogen and vitamin D 3 from a reporter plasmid containing a TGTA element in mammalian cells. This synergy is abolished by mutation of specific amino acids in the ␣2-helix of the histone fold in the conserved C-terminal region of hTAF II 28. Critical amino acids are found on both the exposed hydrophilic face of this helix and the hydrophobic interface with TAF II 18. This ␣-helix of hTAF II 28 therefore mediates multiple interactions required for coactivator activity. We further show that mutation of specific residues in the H1 ␣-helix of TBP either reduces or increases interactions with hTAF II 28. The mutations which reduce interactions with hTAF II 28 do not affect functional synergy, whereas the TBP mutation which increases interaction with hTAF II 28 is defective in its ability to synergistically enhance activation by NRs. However, this TBP mutant supports activation by other activators and is thus specifically defective for its ability to synergize with hTAF II 28.The RNA polymerase II transcription factor TFIID is a multiprotein complex composed of the TATA-binding protein (TBP) and a series of TBP-associated factors (TAF II s) (3, 7). Not only are TAF II s components of transcription factor TFIID, but distinct subsets of TAF II s are also components of the SAGA, PCAF, and TFTC complexes (13,14,21,31,40). For human TFIID (hTFIID), cDNAs for 11 hTAF II s have been characterized (10,16,18,24,25).Genetic and biochemical experiments show that some TAF II s are important for promoter recognition and expression of a subset of promoters (15,38,39), while others are more generally required for transcription in Saccharomyces cerevisiae (2,26,27,29 Expression of hTAF II 28 also potentiates ligand-dependent activation by the AF-2s of many NRs, the most dramatic effects being seen with the receptors for 9-cis retinoic acid (retinoid X receptor), estrogen (estrogen receptor [ER]), and the VDR (22). Deletion analysis showed that coactivator activity required amino acids 150 to 179 in the C-terminal domain of hTAF II 28. Subsequent determination of the three-dimensional structure of the hTAF II 28/hTAF II 18 heterodimer at 2.6-Å resolution by X-ray crystallography indicated that these two proteins interact via a histone fold motif present in the C-terminal domain of hTAF II 28 and in the central region of hTAF II 18 (4). Amino acids 150 to 179 required for coactivator activity form the amphipathic ␣2-helix of the hTAF II 28 histone fold. In the hTAF II 28/hTAF II 18 heterodimer, residues on the hydrophobic face of the ␣2-helix make intermolecular contacts with hTAF II 18, while the residues on the mainly hydrophilic solvent-exposed face are available for mediating interactions with other proteins.Although the ability of hTAF II 28 to act as a transcriptional coactivator did no...

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Human TAFII30 is present in a distinct TFIID complex and is required for transcriptional activation by the estrogen receptor

Cited by 382 publications

References 44 publications

Characterization of Brx, a novel Dbl family member that modulates estrogen receptor action

Characterization of Brx, a novel Dbl family member that modulates estrogen receptor action

Genomics and transcription analysis of human TFIID

Synergistic Transcriptional Activation by TATA-Binding Protein and hTAF_II28 Requires Specific Amino Acids of the hTAF_II28 Histone Fold

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Human TAFII30 is present in a distinct TFIID complex and is required for transcriptional activation by the estrogen receptor

Cited by 382 publications

References 44 publications

Characterization of Brx, a novel Dbl family member that modulates estrogen receptor action

Characterization of Brx, a novel Dbl family member that modulates estrogen receptor action

Genomics and transcription analysis of human TFIID

Synergistic Transcriptional Activation by TATA-Binding Protein and hTAFII28 Requires Specific Amino Acids of the hTAFII28 Histone Fold

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Synergistic Transcriptional Activation by TATA-Binding Protein and hTAF_II28 Requires Specific Amino Acids of the hTAF_II28 Histone Fold