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Query: UNIPROT:P10636 (tau protein)
 5,110 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have isolated the MAP/tau proteins from twice-cycled chick brain microtubule preparations and demonstrated that they are responsible for the nitrocellulose DNA binding activity we and others have measured. Using the isolated MAP/tau proteins we then measured the apparent affinity constant K(app) for the homologous chick DNA interaction and found evidence for two equilibrium affinity classes-a K(app) = 6 x 10(7) M-1, responsible for the bulk of the DNA binding activity and a small (less than 10%) higher affinity K(app) = 10(8) - 10(9) M-1, likely due to sequence specific binding protein species. Using the same chick brain MAP-tau protein, a heterologous interaction with D. melanogaster DNA, was found to possess just the lower affinity class-K(app) = 2 x 10(7) M-1. Under stringent binding conditions we carried out equilibrium nitrocellulose filter binding experiments in a ternary reaction mixture at constant MAP/tau protein and 35S radiolabelled chick DNA concentration using increasing and excess concentrations of competitor DNAs of different sources. The order of competitor strengths found was-chick DNA greater than mouse DNA greater than D. melanogaster = E. coli. DNA. These data and specifically the homologous DNA: protein case being the strongest competitor corroborate our previous studies using total microtubule protein and provide new evidence for a conserved interaction of a small DNA sequence class with MAP/tau protein species. Moreover, these data allow us to conclude that the conserved DNA sequence: MAP/tau protein interactions do not critically depend upon any energetic feature co-involving tubulin for their properties since tubulin is absent from these preparations.
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PMID:High affinity DNA-microtubule associated protein interaction. 164 Sep 36

Yeast transcription factor tau (analogous to vertebrate TFIIIC) interacts specifically with the internal split promoter of tRNA genes. Binding to the two promoter elements (A block and B block) occurs within 30 seconds even when they are separated by a long intervening sequence. Dimethylsulfate protection analysis of contact points between tau and the noncoding strand of a series of internally deleted tRNA3(Leu) genes shows that the specificity of the interaction is not affected by changes in the distance or in the relative helical orientation of the promoter elements. This result is consistent with the results of previous footprinting experiments (Baker, R.E., Camier, S., Sentenac, A. and Hall, B.D., 1987, Proc. Natl. Acad. Sci. USA, 84, 8768-8772). To test if any physical constraint is imposed on the DNA molecule upon tau binding, we analyzed the effect of introducing random single-strand breaks in the noncoding strand of the tRNA gene. Whereas some nicks located in the A block were found to prevent tau binding, no single-strand break in the B block region or in the DNA between the A and B blocks were observed to inhibit or facilitate the binding of tau. We therefore propose that the great flexibility of the tau-tDNA interaction is mostly due to the tau protein itself.
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PMID:On the flexible interaction of yeast factor tau with the bipartite promoter of tRNA genes. 220 49

We have determined the sequences of isoforms of human tau protein, which differ from previously reported forms by insertions of 29 or 58 amino acids in the amino-terminal region. Complementary DNA cloning shows that the insertions occur in combination with both three and four tandem repeats. RNAase protection assays indicate that transcripts encoding isoforms with the insertions are expressed in an adult-specific manner. Transcripts encoding four tandem repeats are also expressed in an adult-specific manner, whereas mRNAs encoding three tandem repeats are expressed throughout life, including in fetal brain. The levels of transcripts encoding the 29 or 58 amino acid inserts were not significantly changed in cerebral cortex from patients with Alzheimer's disease. Antisera raised against synthetic peptides corresponding to these different human tau isoforms demonstrate that multiple tau protein isoforms are incorporated into the neurofibrillary tangles of Alzheimer's disease.
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PMID:Multiple isoforms of human microtubule-associated protein tau: sequences and localization in neurofibrillary tangles of Alzheimer's disease. 248 40

Tau protein is a family of microtubule binding proteins, heterogeneous in molecular weight, that are induced during neurite outgrowth and are found prominently in neurofibrillary tangles in Alzheimer's disease. The predicted amino acid sequences of two forms of tau protein from mouse brain were determined from complementary DNA clones. These forms are identical in their amino-terminal sequences but differ in their carboxyl-terminal domains. Both proteins contain repeated sequences that may be tubulin binding sites. The sequence suggests that tau is an elongated molecule with no extensive alpha-helical or beta-sheet domains. These complementary DNAs should enable the study of various functional domains of tau and the study of tau expression in normal and pathological states.
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PMID:The primary structure and heterogeneity of tau protein from mouse brain. 312 23

Two cDNAs (pLM3c 4.1 and pLM3c 6.1) coding for rabbit cytochrome P450 3c were sequenced. cDNA 4.1 (1768 bp) exhibits an open reading frame from nucleotides 74 to 1576 encoding the 501 amino acid residues of the entire protein. cDNA 6.1 (189 bp) appears to encode the last 24 amino acids. Comparative amino acid sequence analysis indicated that P450 PCN1, PCN2, and HLp from rat and man, were 70, 67, and 73% homologous, respectively, to P450 3c. According to the cytochrome P450 nomenclature, the P450 3c gene is termed P450IIIA4. Comparison of the nucleotide sequences indicated that cDNA 6.1 was 100% homologous to cDNA 4.1. However, whereas a poly(A) tract started 23 nucleotides after the AATAAA consensus sequence in cDNA 6.1, cDNA 4.1 had a 3' untranslated region extending 101 bp beyond the polyadenylation signal, which lacked poly(A). This observation is consistent with the previous finding that both cDNA 4.1 and 6.1 hybridized with two distinct species of poly(A)RNA (1700 and 1850 bases) from rabbit liver. The extreme 3'-end 79-bp fragment of cDNA 4.1 therefore was isolated by subcloning in pUC12 (clone p18-Rsa I) and used to probe Northern blots of poly(A)RNA from control and rifampicin-treated rabbit liver. In contrast to cDNA 4.1 and 6.1, p18-Rsa I cDNA hybridized only with the largest (1850 bases) mRNA species. We conclude that rabbit liver contains two P450 3c mRNA species differing in the length of their 3' untranslated region.
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PMID:Complete sequence of cytochrome P450 3c cDNA and presence of two mRNA species with 3' untranslated regions of different lengths. 334 3

Binding of both synthetic poly(A) and naturally occurring poly(A) (+)mRNA as well as DNA to microtubule protein is mediated by microtubule-associated proteins; tubulin itself is not capable of binding these polymers. Bovine brain microtubule protein from immature animals was found to have a significantly lower capacity to bind poly(A) than microtubule protein from old animals. On the other hand, "old" microtubule protein binds DNA more efficiently than "immature" microtubule protein. Microtubule-associated protein 2 [preferred binding site for DNA] and tau proteins [preferred binding site for poly (A)] are specifically phosphorylated by a microtubule-associated, cAMP-dependent protein kinase. It was found that the affinity of microtubule protein for poly(A) is markedly decreased by autophosphorylation of the protein; in the case of DNA, the decrease in affinity was less. Autophosphorylation of "immature" microtubule proteins diminished the binding capacity for poly(A) to a greater extent than do "old" proteins. Scatchard plot analysis revealed that microtubule-protein possesses two different binding sites for poly(A). The corresponding dissociation constants were found to be increased in the phosphorylated system, but phosphorylation does not appear to alter the total number of binding sites. Compared to immature animals, microtubule protein from "old" bovine brains was found to have a reduced number of binding sites for poly(A), whereas the values of the dissociation constants remain unchanged. In contrast to total microtubule protein and homogeneous microtubule-associated protein 2, only one kind of binding site for poly(A) could be detected in homogeneous tau protein. No influence of different RNA or DNA species on microtubule protein-associated cAMP-dependent protein kinase, adenosine triphosphatase and guanosine triphosphatase activities could be detected.
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PMID:Binding of polyribonucleotides and polydeoxyribonucleotides to bovine brain microtubule protein: age-dependent modulation via phosphorylation of high-molecular-weight microtubule-associated proteins and tau proteins. 614 31

Tau protein is a collection of closely related polypeptides that associate with microtubules in vivo and stimulate their assembly in vitro. Using an affinity-purified antiserum against bovine brain tau protein, we found that the number and amount of tau polypeptides changes dramatically during mouse brain development. The different forms appear to result from changes in tau mRNA since in vitro translation products reflect the qualitative and quantitative changes found in vivo. To study the mRNA and genomic complexity of tau protein, we used tau mRNA, purified from polysomes with tau antiserum, to isolate embryonic mouse tau complementary DNA clones. With these probes we have determined that embryonic tau protein is translated from a 6-kb mRNA that persists throughout brain development.
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PMID:Studies on the expression of the microtubule-associated protein, tau, during mouse brain development, with newly isolated complementary DNA probes. 642 24

Cyclin-dependent kinase, Cdk5, has been identified in neural tissue in connection with neurofilament and tau protein phosphorylation. This report describes the characterization of a 62-kDa protein that copurifies with Cdk5 from rat spinal cord homogenates. Dissociation of the protein from neural Cdk5 is concomitant with a reversible loss in kinase activity. Amino acid sequence information from tryptic peptide fragments was used to clone the complementary DNA from rat brain. A single full-length cDNA was characterized coding for a 67.5-kDa protein (p67). Exogenously expressed p67 stimulated Cdk5 kinase activity in vitro in a dose-dependent manner and when presented as an affinity matrix, selectively adsorbed Cdk5 from a cleared rat brain homogenate. In situ hybridization analysis of E18 rat embryos and adult rat brain demonstrated that p67 transcript expression is restricted to neural tissue. Immunohistochemical staining with an amino-terminal peptide-specific antibody further indicated that p67 is exclusively expressed in neurons. Localization in vivo and in cultured rat hippocampal neurons showed that p67 is highly enriched in axons. We propose that p67, by virtue of its regulation of Cdk5, participates in the dynamics of axonal architecture through the modulation of phosphorylation of cytoskeletal components.
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PMID:Molecular characterization of a neuronal-specific protein that stimulates the activity of Cdk5. 753 2

Exposure to 1 microM colchicine, a microtubule disrupting agent, triggered apoptosis in rat cerebellar granule cells (CGC). Apoptotic nuclei began to appear after 12 h followed by oligonucleosomal DNA laddering, whereas inhibition of the mitochondrial 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide metabolism became significant between 18 and 24 h, when most cells already had apoptotic nuclei. These events were preceded by loss of tau protein and fragmentation of alpha and beta tubulins. Colchicine treatment also caused alterations in Ca2+ responses to chemical depolarization and a moderate, but progressive, increase in the resting intracellular Ca2+ concentration. Nearly all neurons expressed c-Fos after the treatment with colchicine. However, while in part of the cell population c-Fos levels subsequently declined, in the neurons undergoing apoptosis the protein was still expressed, but had an abnormal intracellular localization. An increased expression of the constitutive nitric oxide synthase (NOS-I) was also detected at 12 h and was followed by increased nitrite production. Treatment with 100 nM taxol to stabilize the microtubuli prevented DNA laddering and apoptotic body formation induced by colchicine. In contrast, pretreatment with the N-methyl-D-aspartate receptor-antagonist, MK-801, or L-type Ca2+ channel blockers did not prevent colchicine-induced CGC apoptosis. Inhibitors of NOS were also ineffective in preventing apoptotic body formation and DNA laddering, whereas they delayed the secondary cell lysis. These results support the idea that colchicine-induced cytoskeletal alterations directly initiate the genetic and structural modifications that result in CGC apoptosis.
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PMID:Colchicine induces apoptosis in cerebellar granule cells. 753 89

1. This study is an attempt to examine in vitro the cytochemical changes in hippocampal neurones induced by beta-amyloid protein (beta-AP). 2. The mechanism of cell death, and the vulnerability of different regions of the hippocampus to b-AP toxicity, has also been explored using TUNEL staining to locate fragmented DNA in both dissociated and organotypic cultures. 3. Apoptotic cell profiles and the detection by immunocytochemistry of ubiquitin and tau protein confirmed the acute neurodegenerative effects of b-AP, and organotypic cultures revealed the dentate gyrus to be especially vulnerable. 4. A scrambled sequence of b-AP, a peptide with similar hydrophobic groups to b-AP, and islet pancreatic amyloidogenic peptide also showed neurodegenerative effects, although less severely than b-AP. 5. It is concluded that organotypic cultures provide a valuable in vitro model with which to observe and characterize the neurotoxic effects of b-AP. These effects, however, may be non-specific and related more to the general amyloidogenicity of the b-AP molecule.
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PMID:Neurotoxicity of beta-amyloid protein: cytochemical changes and apoptotic cell death investigated in organotypic cultures. 755 34


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