Disease relevance of S100A10

• RNA interference-mediated silencing of the S100A10 gene attenuates plasmin generation and invasiveness of Colo 222 colorectal cancer cells [1].
• We demonstrated the down-regulation of S100A6 and S100A10 in breast cancer, irrespective of pathological stage [2].
• High expression of calcium-binding proteins, S100A10, S100A11 and CALM2 in anaplastic large cell lymphoma [3].
• Induced transcriptional expression of calcium-binding protein S100A1 and S100A10 genes in human renal cell carcinoma [4].
• This review highlights the important part that S100A10 plays in plasmin regulation and the role this protein plays in cancer cell invasiveness and metastasis [5].

Psychiatry related information on S100A10

• Smith-Magenis syndrome (SMS) is a multiple congenital anomalies/mental retardation syndrome associated with an interstitial deletion of chromosome 17 involving band p11 [6].
• The was a positive correlation between years of training undergone and the amplitude of N20, a negative correlation between the amplitudes of P11 and P13/14 and the number of hours of training undertaken per week, and a positive correlation between the amplitude of N30 and the simple visual reaction time [7].
• The phosphatases P7-P11 were found to be effective in the dephosphorylation of Alzheimer's disease abnormally hyperphosphorylated tau [8].
• A case of schizophrenia-like psychosis (psychotic disorder not otherwise specified according to the DSM-IV criteria) with pericentric inversion on chromosome 9 [inv.(9) (p11; q13)] is reported [9].
• In a series of 127 children diagnosed with autistic disorder the karyotypes of 8, on whom data were available, showed the following chromosomal abnormalities: breakage, a 47 XY pattern, trisomy 13, inversion-duplication of chromosome 15, 47 XY, +der (15) (pter q15: p11 pter), 47 XXY and 46 XY, inv (2) (p11:q13pat, 3q+) [10].

High impact information on S100A10

• Immuno-electron microscopy was performed on human monocytes with immunoglobulins recognizing the active (p20) or precursor (p11) domains of ICE [11].
• Generation of active ICE is affected by the removal of an 11-kD NH2-terminal precursor domain (p11) and an internal 19-amino acid sequence that separates the 20- and 10-kD subunits [11].
• Whole-cell recording in the superficial layers of the developing superior colliculus (sSC) reveals a large drop in NMDA receptor (NMDAR) current decay time synchronized across all neurons and occurring consistently between P10 and P11 [12].
• Active ICE proteins, p10 and p20, were demonstrated by immunoblot in lymphocytes from HIV-1-infected patients and in normal lymphocytes after treatment with Fas agonist, CH11 mAb [13].
• No significant effect on p11 mRNA expression in sigmoid colon or rectum was noted from antidepressant treatment in any of the analyzed subgroups [14].

Chemical compound and disease context of S100A10

• Phl p 11 was expressed as a soluble fusion protein in Escherichia coli, purified to homogeneity and used for serological analysis and to study Phl p 11 specific induction of histamine release from basophils and skin reactivity in sensitized and control subjects [15].
• Both the double virus T7/vaccinia hybrid system and the single recombinant strategy based on the p11 K late promoter were evaluated for their ability to govern expression and secretion of recombinant human secretory component (SC), a glycoprotein associated with IgA in mucosal secretions [16].
• The spin-labeled derivative of podophyllotoxin, N'-podophyllic acid-N-[3-(2,2,5,5-tetramethyl pyrrolinenyloxy)] semicarbazide (GP-11), was synthesized and tested for its antitumor activity against mouse transplantable tumors, Sarcoma-180, Hepatoma-A, P388 leukemia and Ehrlich ascites carcinoma [17].
• In this in vitro study the effects of a range of concentrations (2-10 microg/ml) of sodium selenite were investigated in one low-passage culture of biopsy-derived glioma cells (IPSB-18, an anaplastic astrocytoma, P 18-22) and a normal human brain cell culture (CC2565, P11) [18].
• The effects on intragastric p11 and gastrin secretion of once daily pantoprazole (40 mg) and a new formulation omeprazole (20 mg) in a Multiple Unit Pellet System (MUPS) were investigated during two treatment periods of 7 days each in a randomized crossover study with 16 healthy Helicobacter pylori-negative male volunteers [19].

Biological context of S100A10

• Further, down-regulation of annexin A2 or S100A10 in monocytes by antisense oligodeoxynucleotides impaired the chemotactic response to plasmin, but not that to fMLP [20].
• Antibodies directed against annexin A2 or S100A10 inhibited the chemotaxis elicited by plasmin, but not that induced by fMLP [20].
• In contrast, annexin A2 and S100A10 contain distinct binding sites for plasmin [21].
• We show that siRNA expression mediated by the pSUPER vector causes efficient, stable, and specific down-regulation of S100A10 gene expression [1].
• The phenotype generated by this transient loss-of-protein approach shows for the first time that the annexin 2/S100A10 complex functions in the intracellular positioning of recycling endosomes and that both subunits are required for this activity [22].

Anatomical context of S100A10

• Binding of plasmin to annexin A2 and S100A10 on monocytes was verified by biotin transfer from plasmin labeled with a trifunctional cross-linker [20].
• Typically, S100A10 is thought to be anchored to the plasma membrane via the phospholipid-binding sites of its binding partner, annexin A2 [1].
• Whole-mount immunoelectron microscopy of the aberrantly localized recycling endosomes in annexin 2/S100A10 down-regulated cells revealed extensively bent tubules and an increased number of endosome-associated clathrin-positive buds [22].
• However, these genes were newly expressed in the RCC lesions (n=7) and the RCC cell line, indicating that expression of S100A1 and S100A10 genes is accompanied by RCC [4].
• p11 expression in human bronchial epithelial cells is increased by nitric oxide in a cGMP-dependent pathway involving protein kinase G activation [23].

Associations of S100A10 with chemical compounds

• Of these five amino acids, the first threonine plays a crucial role since the corresponding mutants (TRPV5 T599A and TRPV6 T600A) exhibited a diminished capacity to bind S100A10, were redistributed to a subplasma membrane area and did not display channel activity [24].
• Phosphoinositide specificity of and mechanism of lipid domain formation by annexin A2-p11 heterotetramer [25].
• Epidermal growth factor induces p11 gene and protein expression and down-regulates calcium ionophore-induced arachidonic acid release in human epithelial cells [26].
• Temperature stress-induced annexin 2 translocation is dependent on both expression of protein p11 (S100A10) and tyrosine phosphorylation of annexin 2 because annexin 2 release is completely eliminated on depletion of p11, inactivation of tyrosine kinase, or mutation of tyrosine 23 [27].
• Annexin II heterotetramer (AIIt) is a Ca(2+)- and phospholipid-binding protein that consists of two copies of a p36 and p11 subunit [28].

Physical interactions of S100A10

• To identify components that could regulate differentially the release of pro- and antithrombogenic factors, we analyzed the contribution of Rab3D and the annexin A2/S100A10 complex, proteins implicated in exocytotic events in other systems [29].
• The S100A10 subunit bound t-PA (Kd = 0.45 microm), plasminogen (Kd = 1.81 microm), and plasmin (Kd = 0.36 microm) [21].

Co-localisations of S100A10

• In addition, CEACAM1 co-localized with p11, a component of the tetrameric AIIt complex at the plasma membrane, and with annexin II in secretory vesicles [30].

Regulatory relationships of S100A10

• The mechanism by which annexin A2 regulates the extracellular levels of S100A10 is unknown [5].
• The annexin 2/S100A10 complex controls the distribution of transferrin receptor-containing recycling endosomes [22].
• Immunoprecipitation experiments showed that EGF induced increased p11 binding to cPLA(2) in a time- and dose-dependent manner [26].
• Transient transfection experiments of a reporter gene construct containing 1498 bp of the 5'-flanking region of the p11 promoter demonstrated that IFN-gamma induced p11 gene expression at the transcriptional level [31].
• The fluid-phase recombinant p11 subunit stimulated the rate of t-PA-dependent activation of [Glu]plasminogen about 46-fold compared to an approximate stimulation of 2-fold by the recombinant p36 subunit and 77-fold by recombinant AIIt [32].

Other interactions of S100A10

• Removal of the carboxyl-terminal lysines from the S100A10 subunit attenuated t-PA and plasminogen binding to AIIt [21].
• Comparison of the differentially expressed genes with DNA copy number changes in Karpas299 revealed that two overexpressed genes, S100A10 and S100A11, were located in an amplicon suggesting that the increased mRNA levels were caused by DNA amplification [3].
• Using S100A10 as new bait, a specific interaction with S100A7 was detectable [33].
• Annexin A2-S100A10 heterotetramer, a novel substrate of thioredoxin [34].
• In addition, S100A10 knock-down cells demonstrate a dramatic loss in extracellular matrix degradation and invasiveness as well as reduced metastasis [5].

Analytical, diagnostic and therapeutic context of S100A10

• An electrophoretic mobility shift assay of nuclear proteins extracted from BEAS-2B cells identified an AP-1 site located at -82 to -77 of the p11 promoter region as an NO- and cGMP- dependent response element [23].
• Restriction mapping and sequencing reveals that CLP11 covers a stretch of approx. 11 kb in the human genome [35].
• To map the annexin II-binding site on p11, we have produced progressively truncated p11 derivatives by site-directed mutagenesis [36].
• We show that a corresponding peptide can be used to purify recombinant p11 by affinity chromatography [36].
• An effect on the fibrinolysis pathway after treatment of HUVECs with thrombin was shown by increased fluorescein-labeled plasminogen binding to cells, which was inhibited by an antibody specific for p11 [37].

References