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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Histone acetylation has a key role in transcriptional activation, whereas deacetylation of histones correlates with the transcriptional repression and silencing of genes. Genetic repression may have an important role in neuronal aging, atrophy and degenerative diseases. Our aim was to study how histone deacetylase inhibitors, trichostatin A (TSA) and sodium butyrate, affect the metabolism of cultured rat cerebellar granule neurons and mouse Neuro-2a neuroblastoma cells. Cultured cells were exposed to 1-3 microM TSA and 1-10 mM butyrate for 1-2 days. Both of these inhibitors induced a prominent neuronal apoptosis characterized by morphological changes as well as by the activation of caspase-3 protease and subsequent cleavage of poly(ADP-ribose) polymerase, one of the caspase-3 targets. Caspase-3 activities reached the highest level on the second day after treatment, higher in the proliferating neuroblastoma cells than in the cerebellar granule neurons. Caspase-3 activation and morphological changes were prevented by cycloheximide treatment. Histone deacetylase inhibitors increased the DNA-binding activities of AP1, CREB and NF-kappaB transcription factors. These observations show that an excessive level of histone acetylation induces a stress response and an apoptotic cell death in neuronal cells.
Brain Res Mol Brain Res 1998 Oct 30
PMID:Neuronal apoptosis induced by histone deacetylase inhibitors. 979 19

The adult rat liver is normally in a state of growth arrest. However, cell loss such as partial hepatectomy can induce the proliferation of the hepatocytes. Early after partial hepatectomy, the concentration of p53 mRNA increases during the prereplicative phase. In this study, we identified the cis-regulatory element involved in the induced transcription of the rat p53 gene by DNase I footprinting assay. This element had a partial homology to the AP1 recognition motif, but the competition study with AP1 oligonucleotide showed that this element was not the AP1 recognition motif. The molecular weight of the binding protein to this motif was determined as 39 kDa by southwestern blotting analysis. In vitro transcription assay with the competitor containing the binding motif showed that the 39 kDa protein binding to the element was required for the induced transcription of the rat p53 gene during the liver regeneration.
Biochem Mol Biol Int 1998 Nov
PMID:Transcription of the rat p53 gene is induced by a 39kDa protein binding to the p53 promoter region during the liver regeneration. 984 38

Metallothioneins are small, highly conserved, cysteine-rich proteins that bind a variety of metal ions. They are found in virtually all eukaryotic organisms and are regulated primarily at the transcriptional level. In humans, the predominant metallothionein gene is hMTIIA, which accounts for 50% of all metallothioneins expressed in cultured human cells. The hMTIIA promoter is quite complex. In addition to cis-acting DNA sequences that serve as binding sites for trans-acting factors such as Sp1, AP1, AP2, AP4, and the glucocorticoid receptor, the hMTIIA promoter contains eight consensus metal response element sequences. We report here the cloning of a novel zinc finger protein with a molecular mass of 120 kDa (PZ120) that interacts specifically with the hMTIIA transcription initiation site. The PZ120 protein is ubiquitously expressed in most tissues and possesses a conserved poxvirus and zinc finger (POZ) motif previously found in several zinc finger transcription factors. Intriguingly, we found that a region of PZ120 outside of the zinc finger domain can bind specifically to the hMTIIA DNA. Using transient-transfection analysis, we found that PZ120 repressed transcription of the hMTIIA promoter. These results suggest that the hMTIIA gene is regulated by an additional negative regulator that has not been previously described.
Mol Cell Biol 1999 Jan
PMID:trans repression of the human metallothionein IIA gene promoter by PZ120, a novel 120-kilodalton zinc finger protein. 985 91

As part of a programme to identify seed coat-specific transcripts in pea (Pisum sativum cv. Finale) using the differential display method, we identified and isolated a cDNA encoding a MADS box transcription factor. The predicted peptide contains 247 amino acids with the conserved N-terminal MADS box and is closely related to the AP1/AGL9 subfamily of the MADS box proteins. In addition to weak expression in petals, stamens and carpels, this MADS box mRNA is specifically expressed in the seed coat during seed development.
Plant Mol Biol 1998 Dec
PMID:A MADS box transcription factor of the AP1/AGL9 subfamily is also expressed in the seed coat of pea (Pisum sativum) during development. 986 31

The expression of the human A1 adenosine receptor gene is controlled by two promoters, promoters A and B, and they are located 600 base pairs apart. The characteristics of the two promoters differ by the activity of expression, tissue specificity, and the potential regulatory elements around them. Promoter A is more active but its expression is observed only in selected tissues, whereas promoter B is constitutively expressed but at much reduced levels. In Chinese hamster ovary (CHO) cells transiently transfected with plasmids containing either promoter linked to a reporter gene, dexamethasone (dex) can stimulate (or enhance) the expression of promoter B much more effectively than that of promoter A. Mutation and deletion studies on plasmids containing promoter B have shown that the stimulation is mediated through multiple regulatory sites, including a serum response element, AP1, and TATA box. However, a single-glucocorticoid response element monomer-binding site between promoters A and B does not have significant contribution to dex-regulated expression. The interactions between glucocorticoid receptor (GR) and some regulatory sites are probably occurring via this protein (GR) interacting with other DNA-binding proteins because there is no GR DNA-binding sequence in the sites studied. The stimulation can be eliminated by mifepristone, an antagonist of GR, indicating the involvement of GR in gene regulation. In addition, dex treatment also stimulated the expression of A1 adenosine receptors in CHO cells transfected with the plasmids containing contiguous genomic sequences of promoter B or promoters A and B linked to the receptor-coding sequence. When promoter A is active and both promoter A and B are present in a construct, dex treatment induced a much smaller percentage of stimulation.
Mol Pharmacol 1999 Feb
PMID:Dexamethasone stimulates human A1 adenosine receptor (A1AR) gene expression through multiple regulatory sites in promoter B. 992 23

Homodimeric DNA-binding proteins with relaxed half-site spacing requirements for their DNA targets have been described. As an example, the yeast transcriptional activator Gcn4p binds in vitro equally well to the AP1 site (5'A4T3G2A1C0T1'C2'A3'T4'3') and the ATF/CREB site (5'A4T3G2A1C0G0'T1'C2'A3'T4'3'), which have identical but differently spaced half-site blocks. We describe a novel feature for the bZip class of DNA-binding proteins. The N-14 mutant of a Gcn4p-derived bZip peptide shows a diametrically opposed base-pair recognition specificity depending on the half-site spacing of its DNA target: on pseudo-palindromic, AP1 site-like binding sites, guanine is required in position 2 for proper binding; in contrast, on palindromic, ATF/CREB site-like targets, position 2 must be cytosine to prevent a loss of binding. Modeling studies suggest that the different base-pair requirements on differently spaced DNA targets are due to minimal alterations of the distances between the relevant atoms of the N-14 side-chain and the corresponding target groups on the DNA. Although the N-14 peptide does not have a natural counterpart, its behavior hints at the possibility that dual binding modi dependent on half-site spacing may occur also for natural homodimeric DNA-binding proteins.
J Mol Biol 1999 Mar 05
PMID:A novel feature of DNA recognition: a mutant Gcn4p bZip peptide with dual DNA binding specificities dependent of half-site spacing. 1004 75

The rat p53 promoter has several potential transcription factor-recognition motifs. They include NF1-like, bHLH family, and AP1-like proteins binding sites. The binding protein to NF1-like motif was previously identified. The protein has about 40kDa of molecular mass, which is smaller than that of NF1. Anti-NF1 polyclonal antibody does not recognize the protein. In this study, we isolated the 40kDa protein by sequence-specific DNA affinity chromatography. The isolated protein was assayed by DNase I footprinting analysis. To determine the transactivation effect of the protein, in vitro transcription with the purified 40kDa protein was carried out. After the addition of the purified 40kDa protein into the transcription reaction mixture, the transcription level of the p53 promoter was increased. This suggests that the 40 kDa NF1-like protein is a transcription activator for the rat p53 gene.
Biochem Mol Biol Int 1999 Mar
PMID:In vitro transcription assay with the purified 40kDa NF1-like protein binding to the rat p53 promoter. 1020 79

Eukaryotic vesicular transport requires the recognition of membranes through specific protein complexes. The heterotetrameric adaptor protein complexes 1, 2, and 3 (AP1/2/3) are composed of two large, one small, and one medium adaptin subunit. We isolated and characterized the cDNA for Arabidopsis gamma-adaptin and performed a phylogenetic analysis of all adaptin subunits (proteins) in the context of all known homologous proteins. This analysis revealed (i) that the large subunits of AP1/2/3 are homologous and (ii) two subunits of the heptameric coatomer I (COPI) complex belong to this gene family. In addition, all small subunits and the aminoterminal domain of the medium subunits of the heterotetramers are homologous to each other; this also holds for two corresponding subunits of the COPI complex. AP1/2/3 and a substructure (heterotetrameric, F-COPI subcomplex) of the heptameric COPI had a common ancestral complex (called pre-F-COPI). Since all large and all small/medium subunits share sequence similarity, the ancestor of this complex is inferred to have been a heterodimer composed of one large and one small subunit. The situation encountered today is the result of successive rounds of coordinated gene duplications of both the large and the small/medium subunits, with F-COPI being the first that separated from the ancestral pre-F-COPI.
J Mol Evol 1999 Jun
PMID:Phylogenetic analysis of components of the eukaryotic vesicle transport system reveals a common origin of adaptor protein complexes 1, 2, and 3 and the F subcomplex of the coatomer COPI. 1022 81

Retinoids are therapeutically effective in the treatment of psoriasis, photoaging, acne, and certain cancers. Some of the therapeutic actions of retinoids can be ascribed to retinoic acid receptor (RAR)-mediated antagonism of AP1-dependent gene expression. The increased activity of transcription factor AP1, a complex of oncoproteins Jun and Fos, is associated with cell growth and proliferation. Retinoids, on the other hand, inhibit cell proliferation and affect differentiation, activities that possibly stem from an antagonism of AP1-mediated gene expression by RARs. To gain insight into the molecular mechanism of RAR-AP1 interaction, we have identified the regions of the RAR required for AP1 antagonism. We demonstrate that the AP1 antagonism domain of RAR is a complex of the core of the DNA binding domain and the hydrophobic zipper region. Further, both monomeric RAR and RAR-RXR heterodimers inhibit the expression of an AP1 reporter. CREB binding protein (CBP) has been described as a cofactor for AP1, various nuclear hormone receptor proteins including RARs, and certain other transcription factors and is required for their transactivation properties. Therefore, CBP has been proposed as a common limiting cofactor that can account for inhibition of AP1-dependent gene expression by RARs. Interestingly, however, our results along with previously reported observations suggest that in addition to CBP, there may be other limiting cofactor(s) responsible for mutual transrepression of RAR and AP1.
Mol Cell Biol Res Commun 1999 Apr
PMID:Identification of the AP1-antagonism domain of retinoic acid receptors. 1032 71

Antigen presentation to CD4(+) T lymphocytes requires transport of newly synthesized major histocompatibility complex (MHC) class II molecules to the endocytic pathway, where peptide loading occurs. This step is mediated by a signal located in the cytoplasmic tail of the MHC class II-associated Ii chain, which directs the MHC class II-Ii complexes from the trans-Golgi network (TGN) to endosomes. The subcellular machinery responsible for the specific targeting of MHC class II molecules to the endocytic pathway, as well as the first compartments these molecules enter after exit from the TGN, remain unclear. We have designed an original experimental approach to selectively analyze this step of MHC class II transport. Newly synthesized MHC class II molecules were caused to accumulate in the Golgi apparatus and TGN by incubating the cells at 19 degrees C, and early endosomes were functionally inactivated by in vivo cross-linking of transferrin (Tf) receptor-containing endosomes using Tf-HRP complexes and the HRP-insoluble substrate diaminobenzidine. Inactivation of Tf-containing endosomes caused a marked delay in Ii chain degradation, peptide loading, and MHC class II transport to the cell surface. Thus, early endosomes appear to be required for delivery of MHC class II molecules to the endocytic pathway. Under cross-linking conditions, most alphabetaIi complexes accumulated in tubules and vesicles devoid of gamma-adaptin and/or mannose-6-phosphate receptor, suggesting an AP1-independent pathway for the delivery of newly synthesized MHC class II molecules from the TGN to endosomes.
Mol Biol Cell 1999 Sep
PMID:Early endosomes are required for major histocompatiblity complex class II transport to peptide-loading compartments. 1047 34


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