Disease relevance of SNCG

• However, the molecular targets of SNCG aberrant expression in breast cancer have not been identified [1].
• Similarly, we observed a strong correlation of hypomethylation of the CpG island and SNCG expression in ovarian cancer cell lines (5 of 5) [2].
• When overexpressed, SNCG significantly stimulates breast cancer proliferation and metastasis [2].
• Of the 105 primary gastric cancers, 40 (38.1%) showed apparent SNCG demethylation, similar to the result obtained using cell lines [3].
• SNCG is highly expressed in human-infiltrating breast carcinomas but not expressed in normal or benign breast tissues [4].

Psychiatry related information on SNCG

• Axon pathology in Parkinson's disease and Lewy body dementia hippocampus contains alpha-, beta-, and gamma-synuclein [5].
• The predicted amino acid sequence of BCSG1 gene has a significant sequence homology to the non-amyloid beta protein fragment of the Alzheimer's disease amyloid protein [6].
• The SR protein SC35 is responsible for aberrant splicing of the E1alpha pyruvate dehydrogenase mRNA in a case of mental retardation with lactic acidosis [7].

High impact information on SNCG

• SR proteins serve multiple roles in the posttranscriptional control of gene expression, including as regulators of alternative splicing [8].
• Inactivation of the SR protein splicing factor ASF/SF2 results in genomic instability [9].
• Here we provide evidence that a prototypical SR protein, ASF/SF2, is unexpectedly required for maintenance of genomic stability [9].
• The SR protein SRp38 represses splicing in M phase cells [10].
• SR proteins are highly phosphorylated in vivo, a modification that is required for their function in spliceosome assembly and splicing catalysis [11].

Chemical compound and disease context of SNCG

• The importance of DNA methylation in the control of SNCG expression in cancer cells is further strengthened by demonstration of re-expression of SNCG mRNA in SNCG-negative ovarian and breast cancer cells with a demethylating agent 5-aza-2'-deoxycytidine [2].
• In vivo bisulfite DNA sequencing of genomic DNA isolated from breast cancer cell lines showed that the 15 CpG sites within the CpG island were completely unmethylated in all SNCG-positive cell lines (5 of 5), but were densely and heterogeneously methylated in the majority of SNCG-negative cell lines (3 of 4) [2].
• Moreover, we demonstrate that down-regulation of SNCG expression directly increased the effectiveness of anti-microtubule drug-induced cytotoxicity in breast cancer cells without altering cell responses to doxorubicin [12].
• Accompanied with a reduction of BubR1 protein level, BCSG1 expression resulted in multinucleation of breast cancer cells upon treatment with spindle inhibitor nocodazole, indicating an impaired mitotic checkpoint [13].
• Using mass spectrometry and microsequencing we found adenine phosphoribosyl transferase and breast cancer specific gene 1 (BCSG1) overexpressed in the resistant colorectal tumor cell line [14].

Biological context of SNCG

• In SNCG-nonexpressing ovarian cancer cells, all 15 of the CpG sites were completely methylated instead of selective methylation at certain sites shown in breast cancer cells, thereby suggesting a tissue-specific methylation pattern [2].
• The stimulatory effect of SNCG on ERalpha-regulated gene expression and cell growth can be effectively inhibited by antiestrogens [15].
• Recent studies indicate that synuclein gamma (SNCG) gene, located in chromosome 10, participates in the pathogenesis of the breast and ovary [2].
• In addition, we demonstrate that inhibition of cell growth leads to a decreased mRNA expression and an increased DNA methylation of SNCG gene [2].
• CONCLUSIONS: Aberrant SNCG gene expression can occur via CpG island demethylation, and tends to occur during the more progressive stages of gastric carcinogenesis [3].

Anatomical context of SNCG

• SNCG mRNA was not expressed in the 10 non-neoplastic gastric mucosal tissues, although several CpGs were demethylated [3].
• SNCG demethylation was more frequent in primary gastric cancers positive for lymph node metastasis (51%; 26 of 51) than in cancers without lymph node involvement (26%; 14 of 54; P < 0.05), and also more common in stage II-IV (48%; 27 of 56) than in stage I (27%; 13 of 49) cancers (P < 0.05) [3].
• On late steps of mitosis gamma-synuclein is not found in the centrosomes, and redistributes to the midbody in telophase [16].
• Under stress conditions a translocation of gamma-synuclein from the perinuclear area to the nucleus occurs exhibiting nucleocytoplasmic shuttling. gamma-Synuclein overexpression reduces neurite outgrowth in a greater extent then alpha-synuclein overexpression [16].
• Using transgenic mouse model, we demonstrated a role of SNCG in induction of highly proliferative pregnancy-like phenotype of mammary epithelial cells and branching morphology [17].

Associations of SNCG with chemical compounds

• The SNCG-mediated stimulation of ER-alpha transcriptional activity is consistent with its stimulation of mammary tumorigenesis in response to estrogen [1].
• SNCG expression and methylation status were examined by reverse transcription-PCR and bisulfite-single-strand conformational polymorphism followed by direct sequencing, respectively [3].
• SNCG participated in the heat shock protein-based multiprotein chaperone complex for steroid receptor signaling [17].
• alpha-, beta- and gamma-synuclein are highly homologous proteins that are found predominantly in neurons [18].
• Utilizing human hepatoma-derived cell line HepG2 as an in vitro model, we demonstrate that hepatic carcinogens aflatoxin B1 and N-nitrosodimethylamine (DMN) are strong inducers of SNCG expression [19].

Physical interactions of SNCG

• Here, we demonstrated a chaperone activity of SNCG in the heat-shock protein (Hsp)-based multiprotein chaperone complex for stimulation of estrogen receptor (ER)-alpha signaling [1].

Regulatory relationships of SNCG

• Activation of JNK and its downstream caspase-3 by paclitaxel or vinblastine is significantly down-regulated in gamma-synuclein-expressing cells, indicating that the paclitaxel- or vinblastine-activated apoptosis pathway is blocked by gamma-synuclein [20].
• Further, overexpression of synoretin in retinoblastoma cells up-regulates MAPK and Elk-1 [21].
• AP1 domains in the first intron play an important role in control of BCSG1 transcription [22].

Other interactions of SNCG

• Now, we have also identified gamma -synuclein (SNCG) and a soluble isoform of catechol-o-methyltransferase (s-COMT) as novel candidates for tumor markers in bladder cancer, by means of proteomic analysis [23].
• Urinary CRT, SNCG, and s-COMT were measured as a combined marker by quantitative western blot analysis [23].
• In contrast to paclitaxel and vinblastine, etoposide does not activate JNK, and gamma-synuclein over-expression has no apparent effect on this drug-induced apoptosis [20].
• beta-Synuclein reduces proteasomal inhibition by alpha-synuclein but not gamma-synuclein [24].
• Co-incubating beta-synuclein with gamma-synuclein had no effect on the inhibition of the 20 S proteasome by monomeric gamma-synuclein [24].

Analytical, diagnostic and therapeutic context of SNCG

• In this paper we present data on the localization and properties of gamma-synuclein in several neuronal and nonneuronal cell cultures [16].
• SNCG-induced mammary gland proliferation can be effectively blocked by antiestrogen and ovariectomy, indicating that the induced proliferation is mediated by ERalpha signaling and requires estrogen stimulation [17].
• Gamma-synuclein promotes cancer cell survival and inhibits stress- and chemotherapy drug-induced apoptosis by modulating MAPK pathways [20].
• We studied the expression of alpha-, beta-, and gamma-synuclein in 84 human brain tumors (24 ependymomas, 31 astrocytomas, 8 oligodendrogliomas, and 21 medulloblastomas) by immunohistochemistry [18].
• In this study, we have designed a novel peptide (ANK) and shown its interaction with SNCG using fluorometry, surface plasmon resonance, and isothermal titration calorimetry [25].

References