Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The quantification of mRNA in postmortem human brain is often made complicated by confounding factors. To assess the importance of potential confounders TaqMan real-time RT-PCR was used to measure seven mRNAs (beta-actin, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), cyclophilin, microtubule-associated protein (MAP) 2, neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), amyloid precursor protein (APP) isoform 770) in cortical samples taken from 90 Alzheimer's disease (AD) and 81 control brains. Demographic data for the brain samples were assessed for interaction between factors and amounts of mRNA. Gender was found to play a role in that females had lower levels of mRNA relative to males; this was consistent in both the AD and control brains. Age at death had inconsistent but significant correlations to amounts of mRNA; male and female controls both had negative correlations, female AD a positive correlation and male AD no correlation. Positive correlations were found between brain pH and amount of mRNA in all genes except glial fibrillary acidic protein (GFAP); correlations were consistent across all groupings of pathology and gender. Mean brain pH was significantly lower in AD (6.4) than in control subjects (6.5, ANOVA, p<0.01), though there was no difference between male and females of either group. No correlation was found between brain pH and age at death. Postmortem interval was correlated with brain pH in Alzheimer's disease brains but not controls. Agonal state was generally a poor predictor of mRNA levels whilst inter-lobe variance of mRNA was found to be non-significant in control brains. Given that gender, age at death and brain pH all have significant effects upon mRNA levels it is recommended that these factors be taken into account when quantifying gene expression in postmortem human brain.
Brain Res Mol Brain Res 2003 Oct 21
PMID:Quantifying mRNA in postmortem human brain: influence of gender, age at death, postmortem interval, brain pH, agonal state and inter-lobe mRNA variance. 1455 55

Myosin-Va was identified as a microtubule binding protein by cosedimentation analysis in the presence of microtubules. Native myosin-Va purified from chick brain, as well as the expressed globular tail domain of this myosin, but not head domain bound to microtubule-associated protein-free microtubules. Binding of myosin-Va to microtubules was saturable and of moderately high affinity (approximately 1:24 Myosin-Va:tubulin; Kd = 70 nM). Myosin-Va may bind to microtubules via its tail domain because microtubule-bound myosin-Va retained the ability to bind actin filaments resulting in the formation of cross-linked gels of microtubules and actin, as assessed by fluorescence and electron microscopy. In low Ca2+, ATP addition induced dissolution of these gels, but not release of myosin-Va from MTs. However, in 10 microM Ca2+, ATP addition resulted in the contraction of the gels into aster-like arrays. These results demonstrate that myosin-Va is a microtubule binding protein that cross-links and mechanochemically couples microtubules to actin filaments.
Mol Biol Cell 2004 Jan
PMID:Myosin-Va binds to and mechanochemically couples microtubules to actin filaments. 1456 72

Aurora-A is an oncogenic kinase essential for mitotic spindle assembly. It is activated by phosphorylation and by the microtubule-associated protein TPX2, which also localizes the kinase to spindle microtubules. We have uncovered the molecular mechanism of Aurora-A activation by determining crystal structures of its phosphorylated form both with and without a 43 residue long domain of TPX2 that we identified as fully functional for kinase activation and protection from dephosphorylation. In the absence of TPX2, the Aurora-A activation segment is in an inactive conformation, with the crucial phosphothreonine exposed and accessible for deactivation. Binding of TPX2 triggers no global conformational changes in the kinase but pulls on the activation segment, swinging the phosphothreonine into a buried position and locking the active conformation. The recognition between Aurora-A and TPX2 resembles that between the cAPK catalytic core and its flanking regions, suggesting this molecular mechanism may be a recurring theme in kinase regulation.
Mol Cell 2003 Oct
PMID:Structural basis of Aurora-A activation by TPX2 at the mitotic spindle. 1458 Mar 30

GABARAP and gec1/GABARAPL1 genes encode very similar proteins belonging to a new microtubule-associated protein (MAP) family. These proteins could participate in a complex clustering, targeting and/or degrading the GABA(A) receptors on post-synaptic membrane of neurons. Using specific cDNA probes, we investigated the differential expression of both genes in 76 human tissues. Against all odds, gec1/GABARAPL1 was more expressed than GABARAP in the central nervous system (CNS), while GABARAP was more expressed in endocrine glands.
Brain Res Mol Brain Res 2003 Nov 26
PMID:Expression of gec1/GABARAPL1 versus GABARAP mRNAs in human: predominance of gec1/GABARAPL1 in the central nervous system. 1462 90

Merkel cell carcinoma (MCC) is a rare, aggressive cutaneous carcinoma with neuroendocrine differentiation and a propensity for early spread to regional lymph nodes. Since surgical resection is the mainstay of treatment of MCC, differentiation of MCC from malignant lymphoma, metastatic small cell carcinoma, basal cell carcinoma, and malignant melanoma is very important and is sometimes challenging with routine histologic examination. Immunohistochemical studies may be required to differentiate MCC from other primary and metastatic skin neoplasms. Previously, the authors reported that microtubule-associated protein-2 (MAP-2) is a sensitive and specific marker for pulmonary neoplasms with neuroendocrine differentiation. Because MCC is also a neuroendocrine carcinoma, the authors hypothesized that MAP-2 may be expressed in MCC and therefore may be a useful marker in establishing an accurate diagnosis. MAP-2 staining was demonstrated in all 14 MCCs with diffuse (10 cases) to focal (4 cases) patterns of immunoreactivity. No MAP-2 immunoreactivity was observed in any lymphoma (14 cases), basal cell carcinoma (20 cases), or squamous cell carcinoma (14 cases). CK20 reactivity was present in 12 of 14 cases with focal (2 cases) to diffuse (10 cases) staining having the characteristic perinuclear dot-like pattern. NSE was positive in 13 of 14 cases, SYN was positive in all 14 cases, CHR was positive in 8 of 14 cases, CK7 was positive in 4 of 14 cases, and CD99 was focally positive in 2 cases and diffusely positive in 3 cases. MAP-2 showed a diffuse or focal staining of MCC with a +1 to +4 intensity in most cases. MAP-2 was positive in two cases of MCC that were negative for CK20 and CHR and negative or only slightly positive for SYN and NSE. Therefore, MAP-2 may be a valuable ancillary study in skin tumors suspicious for neuroendocrine origin with faint or negative staining with the antibodies traditionally used for diagnosing MCC. The authors believe this is the first study to demonstrate the utility of MAP-2 in the immunohistochemical workup of MCC. The authors recommend that MAP-2 be added to immunohistochemical panels to confirm the diagnosis of MCC.
Appl Immunohistochem Mol Morphol 2003 Dec
PMID:Diagnostic value of microtubule-associated protein-2 in Merkel cell carcinoma. 1466 58

In Alzheimer's disease (AD), neuronal thread protein (NTP) accumulates in cortical neurons and colocalizes with phospho- tau-immunoreactive cytoskeletal lesions that correlate with dementia. To generate additional information about the potential role of NTP in AD, we characterized its expression and regulation in human SH-Sy5y neuronal cells. Quantitative real-time reverse transcription-polymerase chain reactin and Western blot analysis demonstrated prominent insulin, moderate insulin-like growth factor, type 1 (IGF-1) and minimal nerve growth factor stimulation of NTP expression. In addition, NTP protein was more stable and it progressively accumulated in cells that were stimulated with insulin for 24 or 48 h. Metabolic labeling and phospho-amino acid analysis demonstrated phosphorylation of NTP on Serine residues, 30-60 min after insulin or IGF-1 stimulation, when glycogen synthase kinase 3beta (GSK-3beta) activity would no longer have been suppressed. Kinase inhibitor and in vitro phosphorylation studies demonstrated a role for GSK-3beta in the positive regulation of NTP expression and phosphorylation. Coimmunoprecipitation studies demonstrated physical interactions between NTP and tau or microtubule-associated protein 1b (MAP-1b), and ubiquitin immunoreactivity in NTP immunoprecipitates. In summary, these studies showed that (i) NTP expression is regulated at the level of transcription by insulin and IGF-1 stimulation; (ii) NTP is phosphorylated by GSK-3beta; (iii) NTP can physically interact with tau and MAP-1b and (iv) NTP-MAP complexes are ubiquitinated. The results suggest a functional role for NTP in relation to the turnover or processing of neuronal cytoskeletal proteins, attributes that may be modulated by insulin/IGF-1-mediated signaling.
Cell Mol Life Sci 2003 Dec
PMID:Neuronal thread protein regulation and interaction with microtubule-associated proteins in SH-Sy5y neuronal cells. 1468 91

Che-1 is a recently identified human Rb binding protein that inhibits the Rb growth-suppressing function and regulates cell proliferation. Che-1 contacts the Rb and competes with HDAC1 for Rb-binding site, removing HDAC1 from the Rb/E2F cell cycle-regulated promoters. We have investigated the expression of Che-1 in neuronal cells and we showed that Che-1 directly interacts with Tau. Tau is a microtubule-associated protein involved in the assembly and stabilization of neuronal microtubules network that plays a crucial role modulating neuronal morphogenesis, axonal shape, and transport. In rat cerebellar granule neurons (CGNs) Che-1 partially colocalizes with Tau in the cytoplasm. Che-1 binds the amino-terminal region of Tau protein, which is not involved in microtubule interactions. Tau and Che-1 endogenous proteins coimmunoprecipitate from CGNs cellular lysates. In addition, Che-1/Tau interaction was demonstrated both in overexpressing COS-7 cells and CGNs by FRET analysis. Finally, we observed that Tau/Che-1 interaction is modulated during neuronal apoptosis.
Mol Cell Neurosci 2003 Dec
PMID:Rb binding protein Che-1 interacts with Tau in cerebellar granule neurons. Modulation during neuronal apoptosis. 1469 67

1. Although microtubule-associated protein (MAP) 1B and its phosphorylation have been suggested to be important for synapse formation among cortical neurons, the localization of MAP1B in synapses has not yet been confirmed. In this report, we examine the localization of MAP1B in synaptic regions. 2. The localization of MAP1B was observed by immunohistochemical and electron microscopic techniques using specific antibodies against MAP1B. 3. MAP1B immunoreactivities were widely distributed in the cerebral cortex and were observed in the postsynaptic area but not in presynaptic terminals. 4. These synapses were classified as the asymmetrical type. 5. Only some synapses exhibited MAP1B immunoreactivities. MAP1B-immunopositive synapses accounted for about half of the total synapses. 6. Such a localization suggests MAP1B's important roles in synaptic functions.
Cell Mol Neurobiol 2003 Dec
PMID:Localization of microtubule-associated protein (MAP) 1B in the postsynaptic densities of the rat cerebral cortex. 1496 76

The group of neurodegenerative diseases collectively known as tauopathies are characterized by hallmark lesions consisting of fibrillar aggregates of the microtubule-associated protein, tau (MAPT). Mutations of the tau gene (MAPT) are the cause of frontotemporal dementia with parkinsonism linked to chromosome 17, giving tau a central role in the pathogenic process. The chromosomal region containing MAPT has been shown to evolve into two major haplotypes, H1 and H2, which are defined by linkage disequilibrium (LD) between several polymorphisms over the entire MAPT gene. Studies to date suggest a complete absence of recombination between these two haplotypes. The more common haplotype H1 is over-represented in patients with progressive supranuclear palsy (PSP) and corticobasal degeneration. Using single nucleotide polymorphisms, we mapped LD in the regions flanking MAPT and have established the maximum extent of the haplotype block on chromosome 17q21.31 as a region covering approximately 2 Mb. This gene-rich region extends centromerically beyond the corticotrophin releasing hormone receptor 1 gene (CRHR1) to a region of approximately 400 kb, where there is a complete loss of LD. The telomeric end is defined by an approximately 150 kb region just beyond the WNT3 gene. We show that the entire, fully extended H1 haplotype is associated with PSP, which implicates several other genes in addition to MAPT, as candidate pathogenic loci.
Hum Mol Genet 2004 Jun 15
PMID:The structure of the tau haplotype in controls and in progressive supranuclear palsy. 1511 61

Tau is a neuronal, microtubule-associated protein that stabilizes microtubules and promotes neurite outgrowth. Tau is largely unfolded in solution and presumably forms mostly random coil. Because of its hydrophilic nature and flexible structure, tau complexed to microtubules is largely invisible by standard electron microscopy methods. We applied a combination of high-resolution metal-shadowing and cryo-electron microscopy to study the interactions between tau and microtubules. We used recombinant tau variants with different domain compositions, (1) full length tau, (2) the repeat domain that mediates microtubule binding (K19), and (3) two GFP-tau fusion proteins that contain a globular marker (GFP) attached to full-length tau at either end. All of these constructs bind exclusively to the outside of microtubules. Most of the tau-related mass appears randomly distributed, creating a "halo" of low-density mass spread across the microtubule surface. Only a small fraction of tau creates a periodic signal at an 8 nm interval, centered on alpha-tubulin subunits. Our data suggest that tau retains most of its disordered structure even when bound to the microtubule surface. Hence, it binds along, as well as across protofilaments. Nevertheless, even minute concentrations of tau have a strong stabilizing effect and effectively scavenge unpolymerized tubulin.
J Mol Biol 2004 Jun 04
PMID:Surface-decoration of microtubules by human tau. 1514 41


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