Disease relevance of TAGLN

• Shifted cells undergo a process of cell hypertrophy, as demonstrated by increased time of flight and forward scatter, as well as increased expression of the contractile proteins alpha-smooth muscle actin, myosin light chain kinase, and SM22 [1].
• We performed site-directed mutagenesis to generate a series of NH(2)-terminal histidine (His)-tagged mutants of human SM22 in Escherichia coli and used these to analyze the functional importance of potential actin binding domains [2].
• Contrary to our expectation, SM22 and smooth muscle myosin heavy chain promoter activities (but not viral murine sarcoma virus-long terminal repeat promoter activity) were decreased in long term serum-deprived myocytes by at least 8-fold [3].
• The SMC identity of both pdSMC lines was confirmed by SM22 mRNA expression. pdSMC2 were generally diploid but with various structural and numerical alterations; pdSMC1A demonstrated several chromosomal abnormalities, most commonly -Y, +7, -13, anomalies previously reported in both primary pdSMCs and atherosclerotic tissue [4].
• The following results were observed: The levels of liver fatty acid-binding protein, actin-binding protein/smooth muscle protein 22-alpha and cyclooxygenase 2 were downregulated in colorectal carcinoma compared to normal colon mucosa [5].

High impact information on TAGLN

• The pattern of expression of these two genes contrasted markedly with that of calponin and SM22 alpha, genes expressed predominantly by differentiated smooth muscle cells and whose expression was generally confined to the media of the vessel [6].
• Muscle-specific enzyme isoforms and contractile intermediate filaments including tropomyosin and smooth muscle (SM22) alpha protein were detected in the myoepithelial cells, and a large number of cytokeratin subclasses and isoforms characteristic of luminal cells were detected in this cell type [7].
• Thus, both replicative senescence and forced expression of the WS3-10 gene sequence lead to suppression of Ca(2+)-dependent membrane currents, which suggests that a causal connection exists between these two processes [8].
• Stable transfection of transgelin in LNCaP cells suppressed AR-mediated cell growth and prostate-specific antigen expression, whereas this suppressive effect was abolished by the addition of ARA54-small interfering RNA [9].
• Here we describe transgelin as the first ARA54-associated negative modulator for AR [9].

Chemical compound and disease context of TAGLN

• Among the identified proteins, there were seven over-expressed proteins in stomach cancer tissue: NSP3, transgelin, prohibitin, heat shock protein (hsp) 27 and variant, protein disulfide isomerase A3, unnamed protein product and glucose regulated protein [10].

Biological context of TAGLN

• Expression and cytogenetic localization of the human SM22 gene (TAGLN) [11].
• The SM22 alpha gene has widely been used to study the regulatory mechanisms of smooth muscle cell (SMC) gene expression during cardiovascular development [12].
• To determine whether additional sequences are required for SM22 alpha expression in all subtypes of SMCs, we examined the expression of a bacterial artificial chromosome containing the hSM22 alpha locus in transgenic mice [12].
• We found that cosmid 16b6 contains the entire 5.4-kb, five-exon human SM22 gene (HGMW-approved symbol, TAGLN), and we cytogenetically localized the gene to chromosome 11q23 [11].
• To determine the regulatory mechanisms for the evolutionarily conserved human SM22 alpha (hSM22 alpha) gene, we demonstrated that 445 bp upstream DNA sequences of hSM22 alpha gene exhibited a high transcriptional activity in arterial SMC, not in venous nor in visceral SMCs during embryogensis [12].

Anatomical context of TAGLN

• Human SM22 alpha BAC encompasses regulatory sequences for expression in vascular and visceral smooth muscles at fetal and adult stages [12].
• Immunostains of transiently transfected airway myocytes revealed that full-length NH(2)-terminal FLAG-tagged SM22 colocalizes with actin filaments, whereas FLAG-SM22-(1-151) does not [2].
• Fibroblast transgelin and smooth muscle SM22alpha are the same protein, the expression of which is down-regulated in many cell lines [13].
• RESULTS: On day 3 postadenoviral delivery (infiltration), expression of lacZ (histology, beta-galactosidase) or GFP (fluorescence microscopy) was confirmed across the tissue (CMV and RSV promoters) and exclusively in vascular smooth muscle cells (specific SM22 promoter), without evidence of tissue inflammation [14].
• HeLa cells do not express WS3-10 protein [15].

Associations of TAGLN with chemical compounds

• In addition, four proteins, such as peroxiredoxin 2, transgelin, hippocampal cholinergic neurostimulating peptide (HCNP) and beta-galactoside-binding lectin, were under-expressed in the bladder of BOO group [16].
• Results: We identified several immunoreactive plaques encoding known autoantigens, and several encoding known muscle-related proteins, including aldolase C, eukaryotic translation elongation factor 1 alpha 1, transgelin, and acetyl-coenzyme A acyltransferase 1 [17].
• These data supported that downregulation of HCNP might make detrusor muscle be supersensitive to acetylcholine, up-regulation of optineurin means the protection of nerve injury, and down-regulation of transgelin means the decreased contractility of detrusor muscle [16].

Regulatory relationships of TAGLN

• Here, we investigated the effect of changes in the expression of histone acetyltransferases (HAT) or histone deacetylases (HDAC) on TGFbeta1-induced SM22 promoter activities [18].

Other interactions of TAGLN

• Third, the steady-state level of the mRNA of three senescence-associated genes, i.e. fibronectin, osteonectin and SM22, was increased in HDFs at 72 h after three and five exposures to UVB [19].
• It has structural homology to calponin, but how SM22 binds to actin remains unknown [2].
• Of the three consensus protein kinase C or casein kinase II phosphorylation sites in SM22, only Ser-181 was readily phosphorylated by protein kinase C in vitro, and such phosphorylation greatly decreased actin binding [2].
• TGFbeta1 also stimulates the association of Smad3 (a potent transactivator for the SM22 promoter) and p300 by co-immunoprecipitation assay [18].
• DP III-1 and DP III-2 cDNA clone showed significant homology to the cDNA of alpha actin gene; DP III-3 cDNA clone showed significant homology to the cDNA of transgelin gene [20].

Analytical, diagnostic and therapeutic context of TAGLN

• Protein levels of SM22-alpha and alpha-SMA were also substantially increased by Western blot and immunofluorescence staining [21].
• Purification, characterization, and partial sequence analysis of a new 25-kDa actin-binding protein from bovine aorta: a SM22 homolog [22].
• Here, the distribution patterns of calponin and SM 22 were compared with that of other smooth muscle contractile and cytoskeletal components in the avian embryo using immunofluorescence microscopy and immunoblotting [23].
• RT-PCR showed that cyclic strain increased the gene expression of SMC markers alpha-actin and SM22, indicating that mechanical stimulation induces SMCs to a more contractile phenotype [24].
• Western blot analysis utilizing these antibodies showed that WS3-10 protein is also overexpressed in senescent HDF when compared to young HDF, and in normal fetal lung HDF when compared to SV40-transformed fetal lung HDF [15].

References