| 2000 |
SM22/TAGLN binds actin through multiple regions in its C-terminal domain (residues ~151-201), including a putative actin-binding site (154-KKAQEHKR-161) and residues 170-186. Phosphorylation of Ser-181 by protein kinase C greatly decreases actin binding. A Ser181Asp phosphomimetic mutation also reduced actin binding. Full-length SM22 colocalizes with actin filaments in transfected airway myocytes, while C-terminally truncated SM22-(1-151) does not. |
Site-directed mutagenesis, in vitro cosedimentation assay, PKC phosphorylation assay, immunofluorescence of transfected cells |
Journal of applied physiology |
High |
11053353
|
| 2000 |
SM22/TAGLN is a substrate of protein kinase C (PKC) in vitro. Upon PKC activation in vivo, SM22 dissociates from the actin cytoskeleton and redistributes diffusely in the cytoplasm, indicating that PKC-mediated phosphorylation controls the intracellular localization of SM22. |
In vitro PKC kinase assay on tissue lysate fractions, 2D-gel electrophoresis, mass spectrometry, and in vivo PKC activation with subcellular localization assessment |
Electrophoresis |
Medium |
10939458
|
| 2006 |
SM22/TAGLN represses MMP-9 expression by attenuating ERK/MAPK activation and reducing AP-1 (c-Fos)-dependent transactivation at the proximal MMP-9 promoter. The N-terminal calponin homology domain of SM22 is required for this repressive activity. SM22 overexpression decreased MMP-9 mRNA/protein and reduced in vitro invasion; siRNA knockdown elevated MMP-9; SM22-null mouse uterus showed strong MMP-9 immunoreactivity. |
Expression cloning, siRNA knockdown, MMP-9 promoter deletion and mutagenesis, AP-1 reporter assay, nuclear extract c-Fos binding assay, constitutively active MEK construct, SM22-null mouse immunohistochemistry |
The Journal of biological chemistry |
High |
16835221
|
| 2010 |
SM22 deficiency in vascular smooth muscle cells increases reactive oxygen species (ROS) production (via both mitochondrial and NADPH oxidase contributions linked to p47phox activation), which activates NF-κB2 (p52 pathway) and upregulates proinflammatory genes (Vcam1, Icam1, Cx3cl1, Ccl2, Ptgs2). This was demonstrated in Sm22 knockout mice after carotid denudation injury, in primary Sm22-/- VSMCs, and in PAC1 cells after Sm22 knockdown; ROS scavengers blocked NF-κB activation and proinflammatory gene induction. |
Sm22 knockout mouse carotid denudation model, primary VSMC culture, siRNA knockdown, ROS scavenger experiments, NF-κB activation assays, qRT-PCR, Western blot |
Circulation research |
High |
20224039
|
| 2010 |
SM22 deficiency alters VSMC actin cytoskeleton (compromised stress fiber formation, increased actin dynamics) and promotes chondrogenic conversion after arterial injury, evidenced by upregulation of SOX9, type II collagen, aggrecan, BMP2, and osteopontin, with concomitant suppression of myocardin and VSMC markers. Enhanced ROS production and NF-κB pathway activation mediate SOX9 upregulation in SM22-deficient VSMCs. |
Sm22 knockout mouse carotid denudation model, primary Sm22-/- VSMC culture, VSMC line Sm22 knockdown, actin dynamics assays, gene expression analysis, immunofluorescence |
Cardiovascular research |
High |
21183509
|
| 2008 |
The yeast SM22 homologue Scp1 contains two actin-binding domains that allow it to both bind and bundle actin without dimerization. Scp1 localizes to cortical actin patches during endocytosis. Key residues in the actin interface are required for patch localization. Loss of Scp1 impairs patch movement away from the plasma membrane; double deletion of scp1 and fimbrin/sac6 dramatically increases patch lifetime, establishing a redundant role for actin-bundling proteins in endocytosis. |
Live cell imaging of GFP-tagged mutants, in vitro actin-bundling assays, genetic epistasis (scp1Δ, sac6Δ, double mutant), site-directed mutagenesis of actin-binding domains |
The Journal of biological chemistry |
High |
18400761
|
| 2005 |
Fission yeast Stg1, a SM22/transgelin-like protein, crosslinks F-actin in vitro and localizes to actin patches. Overexpression of Stg1 suppresses contractile ring formation and causes abnormal F-actin aggregates, implicating it in cytokinesis control through actin cytoskeleton regulation. |
Biochemical F-actin crosslinking assay, microscopic localization, overexpression phenotype analysis in S. pombe |
FEBS letters |
Medium |
16256112
|
| 1994 |
A bovine aorta SM22 homolog (25-kDa protein, corresponding to WS3-10) directly binds F-actin at a molar ratio of 1:6 actin monomers with a binding constant of 7.0 × 10^5 M^-1, and associates with the membrane fraction in a Ca2+-sensitive manner (membrane association promoted by Ca2+, dissociated by EGTA). |
Protein purification, F-actin cosedimentation/binding assay, membrane fractionation with Ca2+/EGTA treatment, partial sequence analysis |
Biochemical and biophysical research communications |
Medium |
8117285
|
| 2015 |
SM22 phosphorylation by Rho kinase (ROCK), but not by PKC, negatively regulates SM22-actin binding in smooth muscle cells. Higher phospho-SM22 levels and decreased SM22-actin binding were found in internal anal sphincter (IAS) vs. rectal smooth muscle (RSM) cells. SM22 overexpression caused concentration-dependent relaxation of IAS SMCs greater than RSM SMCs; SM22 siRNA caused contraction in both. This links Rho kinase-mediated SM22 phosphorylation to basal smooth muscle tone regulation. |
pFLAG-SM22 transfection, SM22 siRNA, SMC length measurement, phospho-SM22 western blot, ROCK inhibitor Y-27632 and PKC inhibitor Gö-6850 treatment, SM22-actin binding assay |
American journal of physiology. Gastrointestinal and liver physiology |
Medium |
25617350
|
| 2013 |
TAGLN upregulation in cancer-associated fibroblasts (CAFs) from gastric carcinoma promotes cancer cell migration and invasion in vitro and in vivo. TAGLN knockdown via siRNA in CAFs significantly reduced MMP-2 expression and decreased tumor metastatic capacity, placing TAGLN upstream of MMP-2 in a stromal pro-metastatic pathway. |
siRNA knockdown in CAFs, qRT-PCR, Western blot for MMP-2, transwell migration/invasion assay, in vivo metastasis model |
BMC cell biology |
Medium |
23510049
|
| 2012 |
Depletion of SM22/TAGLN in REF52 fibroblasts disrupts actin organization, increases cell motility, and enables spontaneous podosome formation with increased Matrigel invasion capacity. Conversely, re-expression of SM22 in SM22-negative PC3 prostate cancer cells reduces Matrigel invasion. SM22-depleted cells also show reduced reactive oxygen species levels under serum starvation stress. |
SM22 siRNA knockdown in REF52 fibroblasts, SM22 re-expression in PC3 cells, actin organization assays, podosome scoring, Matrigel invasion assay, ROS measurement under stress |
BMC cell biology |
Medium |
22257561
|
| 2021 |
TRAF6 (an E3 ubiquitin ligase) catalyzes mono-ubiquitination of TAGLN at K89 or K108 residues (with E2 UBE2A/E2A), targeting it for proteasomal degradation. This TRAF6-mediated ubiquitination and degradation of TAGLN leads to activation of NF-κB and Myc signaling pathways. Ablation of TAGLN in prostate cancer cells promoted cell proliferation and suppressed migration. |
In vitro ubiquitination assay screening >20 E2-E3 pairs, site-directed mutagenesis of ubiquitination sites (K89/K108), proteasome inhibitor treatment, TRAF6 overexpression/knockdown, NF-κB and Myc pathway activation assays |
Molecular cancer research |
High |
33771884
|
| 2021 |
TAGLN is expressed in vascular endothelial cells (ECs), where its expression is activated during EC elongation downstream of VEGF-A signaling and PI3K-Akt/mTORC1 pathway inhibition. Genetic disruption of TAGLN (and paralogs TAGLN2, TAGLN3) augmented angiogenic behaviors of HUVECs, identifying TAGLN as a negative regulator of EC elongation and angiogenesis. |
Mouse ESC Tagln promoter-driven fluorescence reporter, VEGF-A treatment, PI3K-Akt/mTORC1 inhibition, HUVEC angiogenesis model, TAGLN/TAGLN2/TAGLN3 CRISPR knockout, immunofluorescence in mouse embryo ECs |
Journal of cell science |
Medium |
34338296
|
| 2021 |
TAGLN acts as a mechanosensitive protein in ovarian cancer cells that responds to extracellular matrix stiffness, forms a regulation loop with Src kinase activation, and mediates stiffness-regulated tumor progression through the RhoA/ROCK pathway. |
Atomic force microscopy (AFM) for stiffness measurement, collagen-coated polyacrylamide hydrogel system for stiffness modulation, transwell assay, immunofluorescence, western blot for RhoA/ROCK pathway, in vivo tumor model |
Journal of experimental & clinical cancer research |
Medium |
34538264
|
| 2021 |
ALKBH5, an m6A RNA demethylase, binds to m6A sites in TAGLN mRNA and reduces its m6A methylation level, thereby inhibiting TAGLN mRNA degradation and increasing TAGLN protein expression. Elevated TAGLN then inhibits enteric neural crest cell proliferation and migration, contributing to Hirschsprung's disease pathogenesis. |
MeRIP-qPCR for m6A site identification, dual-luciferase reporter, ALKBH5 overexpression/knockdown, cell proliferation and migration assays, zebrafish ALKBH5 overexpression model |
Life sciences |
Medium |
33961858
|
| 2020 |
TAGLN physically interacts with HMGA2 (by co-immunoprecipitation), and this complex mediates TGF-β-induced colorectal cancer cell migration and invasion. TGF-β promotes TAGLN protein expression and nuclear translocation. TAGLN knockdown reverses TGF-β-induced EMT (rescues E-cadherin loss, reduces vimentin, fibronectin, MMP9, MMP2); HMGA2 overexpression restores these effects when TAGLN is inhibited, both in vitro and in vivo. |
Co-immunoprecipitation, siRNA knockdown, HMGA2 overexpression, EMT marker western blot (E-cadherin, vimentin, fibronectin), MMP2/MMP9 assay, in vivo tumor model |
OncoTargets and therapy |
Medium |
33116628
|
| 2007 |
The C-terminal domain of SM22α interacts with F-actin. SM22α colocalizes with F-actin during VSMC re-differentiation (serum withdrawal/restimulation). GST pulldown and co-immunoprecipitation confirmed that SM22α interacts with F-actin via its C-terminal domains to participate in cytoskeleton reorganization. |
GST pulldown assay, co-immunoprecipitation, immunofluorescence, F-actin/G-actin fractionation by western blot, prokaryotic expression of GST-SM22α |
Chinese journal of applied physiology |
Medium |
21162287
|
| 2025 |
TAGLN promotes skin fibrosis through a mechano-metabolic axis: TAGLN activates the RhoA/ROCK2 pathway, which in turn upregulates the glucose transporter SLC2A3, thereby promoting glycolysis and enhancing fibroblast motility, contraction, and collagen secretion. Downregulation of TAGLN inhibited fibroblast invasion, migration, contraction, and collagen secretion in vitro, and reduced fibrosis in a bleomycin mouse model. |
Transwell assay, wound healing assay, collagen gel contraction assay, immunofluorescence, RNA-seq, RhoA/ROCK2 pathway inhibition, TAGLN knockdown, bleomycin mouse model |
International journal of biological sciences |
Medium |
39781462
|
| 2025 |
NRF2 directly transcriptionally activates TAGLN expression by binding a functional antioxidant response element (ARE) in the TAGLN promoter, as confirmed by dual luciferase and ChIP assays. TAGLN overexpression promotes ovarian cancer cell migration and EMT (increased N-cadherin, decreased E-cadherin); TAGLN siRNA knockdown in NRF2-overexpressing cells reverses these effects, placing TAGLN downstream of NRF2 in a pro-migratory EMT pathway. |
Dual luciferase reporter assay, chromatin immunoprecipitation (ChIP), TAGLN overexpression, siRNA knockdown, wound-healing assay, Transwell assay, EMT marker western blot |
Journal of ovarian research |
Medium |
41029755
|
| 1987 |
SM22α from chicken gizzard smooth muscle is a 197-residue single polypeptide chain (Mr ~21,978) that exists as a monomer at physiological ionic strengths and is a moderately asymmetric globular protein. Its complete amino acid sequence was determined; no significant homology to previously known proteins was found at the time of publication. |
Automated and manual Edman degradation sequencing, sedimentation equilibrium, CD spectroscopy, Stokes radius determination |
The Journal of biological chemistry |
Medium |
3571244
|