| 1997 |
Sorcin directly inhibits cardiac ryanodine receptor (RyR) open probability (IC50 ~480 nM) and completely inhibits [3H]ryanodine binding (IC50 ~700 nM) when applied to the cytoplasmic side; inhibition is independent of calmodulin/calpain pathways. Phosphorylation of sorcin by the catalytic subunit of PKA significantly decreased its ability to inhibit RyR, placing PKA signaling as an upstream regulator of sorcin's RyR modulatory activity. |
Single-channel recordings of purified RyR, [3H]ryanodine binding assays with recombinant sorcin, in vitro PKA phosphorylation assay |
The Journal of biological chemistry |
High |
9312152
|
| 1995 |
Sorcin undergoes calcium-dependent translocation from the cytosol to cellular membranes. Calcium binding to purified recombinant sorcin at micromolar concentrations induces a conformational change that renders the protein soluble in the non-ionic detergent Triton X-114, suggesting lipids as membrane targets. |
Cell fractionation, detergent-phase partitioning (Triton X-114), calcium-binding assay with purified recombinant sorcin |
FEBS letters |
High |
7835417
|
| 2003 |
Sorcin overexpression in transgenic mouse hearts reduces contraction and relaxation indices, depresses Ca2+ transient amplitudes, and accelerates L-type Ca2+ channel inactivation; sorcin associates with both cardiac RyR and L-type Ca2+ channels. In failing hearts, co-localization of sorcin with RyR at Z-lines is markedly disrupted. |
Transgenic mouse overexpression, in vivo hemodynamics, isolated myocyte Ca2+ imaging, whole-cell patch clamp, Xenopus oocyte expression, co-immunoprecipitation, confocal co-localization |
The Journal of biological chemistry |
High |
12754254
|
| 2015 |
X-ray crystal structures of sorcin in apo and calcium-bound states show that calcium binding to EF1-3 hands drives a large conformational change (movement of the D-helix, opening of EF1) that exposes a hydrophobic pocket. This exposed pocket accommodates sorcin's own N-terminal domain bearing a consensus GYYPGG-like motif and mediates interaction with PDCD6 (a pro-apoptotic penta-EF hand protein carrying the same motif); PDCD6 co-localizes with sorcin in the perinuclear region and midbody. |
X-ray crystallography (apo and Ca2+-bound structures), phage display identification of binding motif, co-localization by fluorescence microscopy |
Scientific reports |
High |
26577048
|
| 2016 |
Sorcin maintains ER Ca2+ stores in pancreatic β-cells by inhibiting ryanodine receptor activity and terminating Ca2+-induced Ca2+ release. Sorcin-null mice are glucose intolerant with impaired glucose-stimulated insulin secretion; β-cell-specific sorcin overexpression under high-fat diet improves glucose tolerance and increases cytosolic and ER Ca2+. Palmitate-induced sorcin downregulation increases G6PC2 levels, contributing to lipotoxicity. |
Sorcin knockout mouse, β-cell-specific transgenic overexpression, glucose tolerance tests, insulin secretion assays, Ca2+ imaging in islets, high-fat diet model, human islet palmitate treatment |
Diabetes |
High |
26822088
|
| 2017 |
Sorcin directly binds doxorubicin, vincristine, paclitaxel, and cisplatin with high affinity. The X-ray structure of the sorcin–doxorubicin complex identifies a binding site at the interface of the EF5 loop, the G helix, and the EF4 loop. Sorcin cellular localization changes upon doxorubicin treatment. Sorcin silencing increases nuclear doxorubicin accumulation, decreases MDR1 expression, and reduces doxorubicin efflux via MDR1. |
Surface plasmon resonance, fluorescence titration, X-ray crystallography (sorcin–doxorubicin complex), confocal microscopy, siRNA knockdown with drug accumulation and efflux assays |
Cell death & disease |
High |
28726784
|
| 2017 |
Sorcin ablation in mice generates an arrhythmogenic substrate: sorcin KO mice develop ventricular arrhythmia and sudden death upon isoproterenol+caffeine challenge. Isoproterenol stimulation causes spontaneous Ca2+ release events in KO cardiomyocytes. Adult KO hearts develop compensatory overexpression of L-type Ca2+ channel and Na+-Ca2+ exchanger, enhancing ICa and INCX and promoting delayed afterdepolarizations. |
Sorcin knockout mouse model, in vivo isoproterenol+caffeine challenge, transverse aortic constriction, Ca2+ imaging in isolated cardiomyocytes, patch clamp (ICa, INCX), Western blot |
Journal of molecular and cellular cardiology |
High |
29174767
|
| 2011 |
Sorcin overexpression confers multidrug resistance in gastric cancer cells and decreases intracellular vincristine concentration; sorcin overexpression upregulates P-glycoprotein (P-gp/MDR1) expression, and P-gp inhibition with verapamil partially reverses sorcin-mediated MDR. |
Gene transfection overexpression, antisense oligonucleotide knockdown, intracellular drug accumulation assay, Western blot, P-gp inhibitor rescue experiment |
Oncology reports |
Medium |
21109982
|
| 2013 |
Sorcin depletion in MDA-MB-231 breast cancer cells reduces the CD44+/CD24- and ALDH1high cancer stem cell pool, reduces mammosphere-forming capacity, induces an epithelial-like phenotype by modulating E-cadherin and VEGF expression, and suppresses metastasis in nude mice. |
RNAi knockdown (transient and stable), lentiviral overexpression, flow cytometry for CSC markers, mammosphere assay, Western blot for EMT markers, in vivo xenograft metastasis assay |
Breast cancer research and treatment |
Medium |
24337682
|
| 2023 |
Sorcin directly binds EGFR in a calcium-dependent manner, controls EGFR proteostasis and signaling, and increases EGFR phosphorylation, leading to increased EGF-dependent cell migration and invasion. Sorcin silencing cooperates with EGFR inhibitors to reduce migration. |
Co-immunoprecipitation, Western blot, siRNA knockdown, migration/invasion assays, EGFR inhibitor combination studies |
Cellular and molecular life sciences : CMLS |
Medium |
37442828
|
| 2023 |
Sorcin interacts with the NLRP3 inflammasome (demonstrated by co-immunoprecipitation and immunofluorescence) and negatively regulates pyroptosis in hepatocellular carcinoma cells; sorcin knockdown activates Caspase-1-dependent pyroptosis and suppresses HCC tumor growth in vivo. |
Co-immunoprecipitation, immunofluorescence, siRNA knockdown, NLRP3 inhibitor (MCC950) and Caspase-1 inhibitor (VX765) rescue, in vivo xenograft |
Cell death & disease |
Medium |
37833249
|
| 2021 |
Sorcin overexpression increases ATF6 transcriptional activity in HEK293 cells, while sorcin knockout reduces ATF6 transcriptional activity and increases ER stress markers, indicating sorcin promotes the protective ATF6-branch of the unfolded protein response. |
Sorcin overexpression, CRISPR/siRNA knockout in HEK293 cells, ATF6 transcriptional reporter assay, Western blot for ER stress markers |
FEBS letters |
Medium |
33960419
|
| 2025 |
Sorcin interacts with PAX5 in the cytoplasm and inhibits PAX5 nuclear translocation; disrupting the sorcin-PAX5 interaction (by the natural product celastrol binding to Cys194 of sorcin) promotes PAX5 nuclear translocation, increases FBXL12 expression, enhances ALDH1A1 ubiquitination, and induces ferroptosis in pancreatic cancer cells. |
Co-immunoprecipitation, ChIP, luciferase reporter, proteomics, surface plasmon resonance, in vivo xenograft with genetic/pharmacological rescue |
Journal of hematology & oncology |
Medium |
40055736
|
| 2024 |
Sorcin interacts with STAT3 (demonstrated by co-immunoprecipitation and immunofluorescence) and activates the NF-κB signaling pathway, thereby inhibiting mitochondrial apoptosis in hepatocellular carcinoma; sorcin knockdown reduces NF-κB activity and increases apoptosis in vitro and in vivo. |
Co-immunoprecipitation, immunofluorescence, Western blot for NF-κB pathway components, mitochondrial membrane potential assay, siRNA knockdown, in vivo xenograft |
International journal of molecular sciences |
Medium |
39000312
|
| 2020 |
Proteomic peptide phage display identified a peptide from protein phosphatase 1 regulatory subunit 3G (PPP1R3G) as a calcium-dependent Sorcin-binding partner, with confirmation by biophysical assays and cell-based approaches, revealing a potential link between glucose homeostasis and calcium concentration. |
Proteomic peptide phage display (ProP-PD), biophysical binding assays, cell-based interaction assays, molecular dynamics simulations |
Biochimica et biophysica acta. General subjects |
Low |
32305337
|
| 2024 |
NMR backbone resonance assignment of full-length sorcin in the calcium-free state reveals that most of the N-terminal domain is disordered; secondary structure prediction from chemical shifts provides a structural foundation for studying Ca2+ sensing by full-length sorcin. |
Solution NMR (1H, 13C, 15N backbone resonance assignment), TALOS+/CSI 3.0 secondary structure prediction |
Biomolecular NMR assignments |
Low |
39215797
|
| 2025 |
Stopped-flow light scattering showed that calcium-induced sorcin aggregation is reversible, cooperative, and primarily concentration-dependent rather than directly determined by physiological calcium levels, suggesting sorcin's calcium sensitivity is tuned by its expression level. |
Stopped-flow light scattering, calcium-titration aggregation assay with purified recombinant sorcin |
The Biochemical journal |
Low |
41133884
|
| 2024 |
Sorcin forms a positive feedback loop with STAT3 to increase transcription of serpin E1 and CCL5, and sorcin overexpression induces pancreatic β-cell dysfunction; sorcin-driven secretion of serpin E1 and CCL5 contributes to pancreatic cancer-associated new-onset diabetes. |
In vitro sorcin overexpression in β-cell lines, co-IP, STAT3 pathway inhibition, cytokine measurement, in vivo mouse model |
Experimental & molecular medicine |
Low |
39516378
|
| 2025 |
Sorcin knockout (Sri-/-) mice display impaired lung alveolarization, reduced surfactant protein expression (Sp-b, Sp-c, Abca3), type II pneumocyte immaturity, and reduced EGFR, RAS, and RAB5C protein levels, implicating sorcin in EGFR-linked lung morphogenesis and surfactant protein recycling. |
Sorcin knockout mouse model, histology, real-time PCR, Western blot, confocal microscopy |
Cellular and molecular life sciences : CMLS |
Medium |
41148307
|