Disease relevance of TAF1

• Preincubation of the ts13 nuclear extracts did not affect the function of several GAL4-activation domain fusion proteins (GAL4-VP16, GAL4-p65, and GAL4-p53) on either the adenovirus major late or cyclin D1 core promoter bearing GAL4 sites, further indicating that the effect of the TAF(II)250 mutation is both core promoter and activator specific [1].
• The NH(2)-terminal kinase domain of TAF(II)250 was sufficient for TFIIA phosphorylation, and this activity was inhibited by full-length retinoblastoma protein but not by a retinoblastoma protein mutant defective for TAF(II)250 interaction or tumor suppressor activity [2].
• Cell cycle gene expression and E2F transcription factor complexes in human melanoma cells induced to terminally differentiate [3].
• Cell cycle gene regulation in reversibly differentiated new human hepatoma cell lines [4].
• Cell-cycle gene expression in lovastatin-induced medulloblastoma apoptosis [5].

High impact information on TAF1

• Our findings suggest that targeted histone acetylation at specific promoters by TAF(II)250 may be involved in mechanisms by which TFIID gains access to transcriptionally repressed chromatin [6].
• The TAF(II)250 subunit of TFIID has histone acetyltransferase activity [6].
• These findings suggest that the targeted phosphorylation of RAP74 by TAFII250 may provide a mechanism for signaling between components within the initiation complex to regulate transcription [7].
• Here, we report that purified recombinant TAFII250 is a protein serine kinase that selectively phosphotylates RAP74 but not other basal transcription factors or common phosphoacceptor proteins [7].
• We show here that the N-terminal A/B region of the ER contains an independent constitutive activation function (TAF-1) that exhibits cell type specificity since it activates transcription efficiently in chicken embryo fibroblasts, but only poorly in HeLa cells [8].

Chemical compound and disease context of TAF1

• MAb 9.2.27 (IgG2a) directed against a chondroitin sulfate proteoglycan and its core protein with a molecular weight of 250,000 (p250) on human melanoma cells did not mediate antibody-dependent cell-mediated cytotoxicity [9].
• Hyperthermia and photoactivated hematoporphyrin derivative induce a dose-dependent reduction in the expression of the p250 surface melanoma-associated antigen on the human FME cell line [10].

Biological context of TAF1

• Thus, phosphorylation and the resultant degradation of p53 provide a mechanism for regulation of the cell cycle by TAF1 [11].
• The largest subunit of TFIID, TAF1, possesses an intrinsic protein kinase activity and is important for cell G1 progression and apoptosis [11].
• Furthermore, both RNAi-mediated TAF1 ablation and apigenin-mediated inhibition of the kinase activity of TAF1 markedly reduced Thr-55 phosphorylation [11].
• These data have led us to hypothesize that TAF1-dependent histone acetylation facilitates transcription factor binding to the Sp1 sites, thereby activating cyclin D1 transcription and ultimately G(1)-to-S-phase progression [12].
• A missense mutation within the histone acetyltransferase (HAT) domain of the TATA binding protein-associated factor TAF1 induces ts13 cells to undergo a late G(1) arrest and decreases cyclin D1 transcription [12].

Anatomical context of TAF1

• The TAFII250 subunit of the human transcription factor IID (TFIID) rescues the temperature-sensitive hamster cell line ts13 and overcomes a G1 arrest [13].
• Here we present a novel autosomal human gene, TAF1L, which is homologous to TAF(II)250 and is expressed specifically in the testis, apparently in germ cells [14].
• Both NFPC and TAF1 function in cell-cell adhesion in the neural ectoderm, and disruptions in either NFPC or TAF1 result in a failure of the neural tube to close [15].
• Studies of expression in normal tissues demonstrated expression of NSCL-1 and NSCL-2 in the developing central and peripheral nervous system, most likely in developing neurons [16].
• Labeling with these two antibodies has documented that NUP153 is a constituent of the nuclear basket with at least one of its epitopes residing in its terminal ring, whereas p250 is a constituent of the cytoplasmic filaments [17].

Associations of TAF1 with chemical compounds

• Substitution of Thr-55 with an alanine residue (T55A) stabilizes p53 and impairs the ability of TAF1 to induce G1 progression [11].
• The hypoacetylation of H3 at the cyclin D1 promoter was reversed by treatment with trichostatin A (TSA), a histone deacetylase inhibitor, or by expression of TAF1 proteins that retain HAT activity [12].
• Estrogen functions as an ER agonist by promoting functional synergism between TAF1 and TAF2 [18].
• The largest subunit of the human transcription factor TFIID, TAFII250, was previously reported to contain serine/threonine kinase domains that can autophosphorylate and transphosphorylate the large subunit of the basal factor TFIIF [19].
• In the presence of RU486 TAF-2 was inactive, while TAF-1 within the hPR form B/RU486 complex activated transcription from a reporter gene containing a single palindromic PRE [20].

Physical interactions of TAF1

• TAF(II)55 binding to TAF(II)250 inhibits its AT activity [21].
• Moreover, c-Jun blocked the repression of TBP DNA binding caused by the N terminus of TAF(II)250 [22].
• However, we found no evidence of TAFII250-binding competition between Rb and cyclin D1 in vitro [23].
• CCG1 contains a sequence similar to the putative DNA-binding domain of HMG1 in addition to the previously detected amino acid sequences common in nuclear proteins, such as a proline cluster and a nuclear translocation signal [24].
• The factor hCIA interacts with hCCG1 and functions as a histone chaperone in mammalian cells; its homologue in yeast is Asf1p/Cia1p [25].

Enzymatic interactions of TAF1

• TAF1 interacts with and phosphorylates p53 at Thr-55 in vivo [11].

Regulatory relationships of TAF1

• Thus, TAF(II)55 is capable of regulating TAF(II)250 function by modulating its AT activity [21].
• We found that TAF1 induces G1 progression in a p53-dependent manner [11].
• We further found that the Rb-related protein p107 can inhibit TAFII250 kinase activity, and this inhibition is likewise alleviated by cyclin D1 [23].
• Expression of wild-type TAF(II)250 in tsBN462 stimulates and prolongs the synthesis of Mdm2 and rescues the temperature-sensitive phenotype [26].

Other interactions of TAF1

• Comparative far Western blots have shown that hTAF(II)135 interacts strongly with hTAF(II)20, moderately with hTAF(II)150, and weakly with hTAF(II)43 and hTAF(II)250 [27].
• USF1 augments transcription initiating through the upstream start sites and is dependent on TAF1 (TAF(II)250), a finding consistent with its role in regulating basal class I transcription [28].
• Transcription of a chimeric promoter containing the Sp1 sites of cyclin D1 and c-fos core remained TAF1 dependent in ts13 cells [12].
• Temperature-dependent DNA binding activity is also observed for TAF1-TAF2 heterodimers assembled with the ts13 mutant but not the wild-type TAF1 protein [29].
• Moreover, transcription from the cyclin A and cdc2 promoters becomes impaired when cotransfected with hTAFII250 containing inactive forms of the N-terminal kinase domain [19].

Analytical, diagnostic and therapeutic context of TAF1

• Chromatin immunoprecipitation assays revealed that histone H3 acetylation was reduced at the cyclin D1 promoter but not the c-fos promoter upon inactivation of TAF1 in ts13 cells [12].
• Molecular cloning of the cDNA of human X chromosomal gene (CCG1) which complements the temperature-sensitive G1 mutants, tsBN462 and ts13, of the BHK cell line [30].
• Gel filtration experiments demonstrate that CIF150 (hTAF(II)150) seems to be less tightly associated with human transcription factor IID than hTAF(II)130 is associated with hTAF(II)250 [31].
• The P250 potential which corresponded to the N250m-P250m was clearly identified, probably because activation of multiple areas generated large long-duration EEG potentials which were maximal around the vertex, unlike MEG recordings [32].
• A monoclonal antibody, termed QE5, recognized three NPC polypeptides, p250, NUP153, and p62 on Western blots, and labeled the nuclear envelope of several cultured cell lines by immunofluorescence microscopy [17].

References