Disease relevance of S100B

• S100B protein is elevated in the brains of patients with early stages of Alzheimer's disease and Down's syndrome [1].
• S100 calcium-binding proteins such as S100B are elevated in primary malignant melanoma and are used as markers for this and numerous other cancers [2].
• Collectively, these findings imply that elevated levels of S100B in tumors such as astrocytomas and gliomas could inhibit p53 functions and contribute to cancer progression [3].
• There was a significant trend for increasing S100B levels from PP to SP to RR multiple sclerosis (P < 0.05) [4].
• We also provide evidence that, in human astrocytoma cell lines, S100B co-localizes with IQGAP1 at the polarized leading edge and areas of membrane ruffling and that both proteins relocate in a Ca(2+)-dependent manner within newly formed vesicle-like structures [5].
• Enteric glial-derived S100B is increased in the duodenum of patients with celiac disease and plays a role in nitric oxide production [6].

Psychiatry related information on S100B

• With regard to psychopathology, negative symptomatology appears to be the predicting factor for the absolute S100B concentration [7].
• However, we observed a decrease in the cerebrospinal fluid S100B after the critical period for synaptogenesis in rodents [8].
• The hypothesis that the overexpression of S100B in Alzheimer brain is related to the progression of clinical symptoms was addressed in living persons by measuring S100B concentrations in cerebrospinal fluid (CSF) from AD patients with a broad range of clinical dementia severity and from healthy older persons [9].
• S100B was positively correlated with the subscore 'thought disturbance' of the Brief Psychiatric Rating Scale (p<0.05) [10].
• S100B is increased in mood disorders and may be reduced by antidepressive treatment [11].

High impact information on S100B

• Gene encoding the beta subunit of S100 protein is on chromosome 21: implications for Down syndrome [12].
• Genomic and complementary DNA probes were used in conjunction with a panel of rodent-human somatic cell hybrids to assign the gene for the beta subunit of S100 protein to the distal half of the long arm of human chromosome 21 [12].
• Severe immunodeficiency associated with a human immunodeficiency virus 1 NEF/3'-long terminal repeat transgene [13].
• In the present report, we show that HIV-specific CTL responses can also be detected in lymph nodes and spleens, and were mainly directed against the ENV, GAG, and NEF HIV-1 proteins [14].
• Carboxyl-terminal and central regions of human immunodeficiency virus-1 NEF recognized by cytotoxic T lymphocytes from lymphoid organs. An in vitro limiting dilution analysis [14].

Chemical compound and disease context of S100B

• We next characterized AHNAK as a major Ca(2+)-dependent S100B target protein in the rat glial C6 and human U-87MG astrocytoma cell lines [15].
• METHODS: Formalin-fixed, paraffin-embedded archival tissues were evaluated by immunohistochemistry using antibodies specific for S100A6 and S100B in 38 intradermal nevi (IDN) [16].
• In somatic cell hybrids produced between the C8161 and a group of non-metastatic human melanoma lines which exhibited melanocyte differentiation markers including S100, HMB-45, NKI/C3, and melanin, the fusions were uniformly metastatic and undifferentiated [17].
• Amyotrophic lateral sclerosis: disease stage related changes of tau protein and S100 beta in cerebrospinal fluid and creatine kinase in serum [18].
• To clarify the effects of hyperglycemia on O(2)(-) generation, normal human monocytes were treated with receptor for advanced glycation endproducts (RAGE) ligands (AGE protein and S100B) or high glucose media before stimulation [19].

Biological context of S100B

• But, the differences in the way these proteins bind to p53 could result in S100B and S1004 having different effects on p53 function in cell-cycle control [1].
• The molecular definition of the monosomy 21 in each patient was, respectively, COL6A1-S100B, CD18-S100B, and PFKL-S100B [20].
• Comparison to databases indicated three segments matching to known chromosome 21 genes: PFKL, COL6A1 and S100B and six segments matching to unmapped anonymous expressed sequence tags (ESTs) [21].
• NMR spectroscopy revealed residues most responsive to TRTK-12 binding that could be mapped to the surface of the three-dimensional structure of calcium-saturated S100B, revealing a common region indicative of a binding site [22].
• Expression of S100B protein in E. coli results in little change in FtsZ protein levels, causes a filamenting bacterial phenotype characteristic of FtsZ inhibition, and leads to missed rounds of cell division [23].

Anatomical context of S100B

• Cell-based and clinical studies have implicated S100B in the initiation and maintenance of a pathological, glial-mediated proinflammatory state in the central nervous system [24].
• In glial cells, a relationship exists between cytoplasmic S100B accumulation and cell morphological changes [5].
• The synthetic peptide TRTK-12 (TRTKIDWNKILS), derived from random bacteriophage library screening, bears sequence similarity to several intermediate filament proteins and has the highest calcium-dependent affinity of any target molecule for S100B to date (K(d) <1 microm) [25].
• This signaling was inhibited in cells pretreated with soluble RAGE, and S100B was shown to bind to chondrocyte RAGE [26].
• Our results may explain the rescue of nuclear wild type p53 activities by S100B in fibroblast cell lines expressing the temperature-sensitive p53val135 mutant at the nonpermissive temperature [27].

Associations of S100B with chemical compounds

• We have identified the IQGAP1 protein as the major cytoplasmic S100B target protein in different rat and human glial cell lines in the presence of Zn(2+) and Ca(2+) [5].
• The Zn(2+)- and Ca(2+)-binding S100B protein is implicated in multiple intracellular and extracellular regulatory events [5].
• A pull-down assay using biotin-labeled S100B was used to demonstrate binding to RAGE [26].
• Here, we probed the putative causal relationship between enhanced astrocytic activation and exacerbation of brain damage in 4/4-KI mice using arundic acid (ONO-2506, Ono Pharmaceutical Co. Ltd), which is known to oppose astrocytic activation through its inhibitory action on S100B synthesis [28].
• These contributions were quantified using C-terminal mutant S100B proteins lacking the C-terminal seven (S100B85stop) or nine (S100B83stop) residues or containing alanine substitutions at Phe87 (F87A), Phe88 (F88A), or both (F8788A) [29].

Physical interactions of S100B

• AHNAK binds to S100B-Sepharose beads and is also recovered in anti-S100B immunoprecipitates in a strict Ca(2+)- and Zn(2+)-dependent manner [15].
• S100A6 and S100A11 are specific targets of the calcium- and zinc-binding S100B protein in vivo [30].
• Furthermore, p53 binds regions of the S100B promoter, one of which matches the 20-nucleotide p53-binding consensus DNA sequence perfectly [2].
• S100B is an EF-hand containing calcium-binding protein of the S100 protein family that exerts its biological effect by binding and affecting various target proteins [31].
• The crystal structure of human EF-hand calcium-binding protein S100A12 in its calcium-bound form has been determined to 1.95 A resolution by molecular replacement using the structure of the S100B protein [32].
• More importantly, we showed that S100B and S100A6 modulate cell survival in a RAGE-dependent manner; S100B specifically interacted with the RAGE V and C(1) domains and S100A6 specifically interacted with the C(1) and C(2) RAGE domains [33].

Co-localisations of S100B

• In the peripheral sciatic nerve, nectin-3 immunoreactivity was observed both in controls and following injury and nectin-3 colocalized with both neurofilament and the Schwann cell marker S100 [34].

Regulatory relationships of S100B

• Zn(2+) binding to S100B is sufficient to promote interaction with IQGAP1 [5].
• Administration of S100B before TMT treatment prevented TMT-induced changes in morphology and GFAP expression [35].
• Nevertheless, S100A10 is predominantly expressed in certain types of neurons whereas S100B is more abundant in glia [36].
• In contrast, S100B stimulated phosphoglucomutase activity in a calcium-dependent manner [37].
• S100B pretreatment blocked the TMT-induced increase in TNF-alpha expression in microglia [35].

Other interactions of S100B

• Very significant modifications occurred in the level of S100A1 protein expression (and, to a lesser extent, in their of the S100A4 and S100B proteins) in relation to the increasing levels of malignancy [38].
• There was a correlation between GFAP levels and ambulation in SP multiple sclerosis (r = 0.57, P < 0.01), and between S100B level and the 9HPT in PP multiple sclerosis patients (r = -0.85, P < 0.01) [4].
• In this report, we show that the S100B protein decreases p53 DNA binding and transcriptional activity [3].
• They also reveal an additional cellular function for IQGAP1 associated with Zn(2+)/Ca(2+)-dependent relocation of S100B [5].
• These results suggest that the effects of S100A1 and S100B are not nonspecific effects of low molecular weight, acidic proteins [37].

Analytical, diagnostic and therapeutic context of S100B

• Calcium-dependent physical interaction between S100B and FtsZ was demonstrated in vitro by affinity chromatography, and this interaction was severely inhibited by the competitor peptide TRTK-12 [23].
• Down-regulation of p53 in primary malignant melanoma cells is likely the result of a direct interaction with S100B, which was observed by co-immunoprecipitation experiments [2].
• While the nature of the exact targets for S100B has yet to be defined, random bacteriophage peptide mapping experiments have elucidated a calcium-sensitive "epitope" (TRTK-12) for S100B recognition [22].
• By Northern and Western blotting, S100B and S100A6 were shown to be expressed at high levels in a panel of human melanoma cell lines [39].
• S100B serum levels (quantitative immunoassay) and psychopathology (Positive and Negative Syndrome Scale, PANSS) were examined upon study admission and after 12 and 24 weeks of standardized treatment in 98 chronic schizophrenic patients with primarily negative symptoms [7].

References