Identification, localization and characterization of the human γ-synuclein gene

Lavedan, Christian; Leroy, Elisabeth; Dehejia, Anindya; Buchholtz, Stephanie; Dutra, Amalia; Nussbaum, Robert L.; Polymeropoulos, Mihael H.

doi:10.1007/s004390050792

Cited by 171 publications

(153 citation statements)

References 24 publications

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“…These repeats result in the formation of conserved amphipathic A2-helices also characteristic of apolipoproteins, which mediate reversible binding to phospholipid membranes. This property supports the role of synucleins in vesicular release at presynaptic nerve terminals (1)(2)(3)(4). Although their normal cellular functions have not been clearly defined, synucleins have attracted considerable attention due to their involvement in neurodegenerative diseases.…”

Section: Introductionsupporting

confidence: 65%

Expression of α-, β- and γ-synuclein in colorectal cancer, and potential clinical significance in progression of the disease

Wang²,

Peng³

et al. 2009

Oncol Rep

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Abstract. The synucleins (·-, ß-and Á-synuclein) are a small, soluble, highly conserved group of neuronal proteins that attracted considerable attention due to their involvement in both neurodegenerative diseases and cancer. In this study, we examined the synuclein exprsssion in colorectal cancer (CRC) tissues, tumor-matched non-neoplastic adjacent tissues (NNAT), and CRC cell lines, and then investigated clinical significance of synucleins. By using semi-quantitative RT-PCR, synuclein mRNA expression was detected in eight CRC cell lines. It was much higher in CRC samples than in NNAT samples (P<0.05). The results of Western blotting showed that the levels of synucleins protein expression in CRC cells approximately corresponded to the levels of synuclein mRNA expression. Immunohistochemical staining revealed that Á-synuclein protein expression was up-regulated in CRC samples compared to NNAT samples (P=0.022), and was significantly correlated with clinical stage and lymph node involvement of CRC (P<0.05). Although, there was no significant difference in either ·-or ß-synuclein protein expression between tumor and normal samples (P>0.05), often more than one form of synuclein was expressed in a tumor sample. More ratios of later stage and lymph node-positive tumors expressed a least one type of synuclein protein, and more ratios showed positive for either · or Á-synuclein expression, as well as positive either for ß or Á-synuclein in more ratios of lymph node-positive tumors. These results show that ·-, ß-and Á-synuclein are expressed in a high percentage of CRC. Á-synuclein protein is valuable for evaluation of progression of CRC, and it is more sensitive to predict advanced stage and lymph node invasion by detection of Á-synuclein protein combined with either ·-or ß-synuclein protein or both than by detection of Á-synuclein only. IntroductionThe synucleins are a family of small, soluble, highly conserved neuronal proteins that consist of ·-, ß-, and Á-synuclein. They are a natively unfolded group of proteins that are characterized by 5-6 repeats of amino acid motif (KTKEGV), constituting most of the N-terminal half of the proteins. These repeats result in the formation of conserved amphipathic A2-helices also characteristic of apolipoproteins, which mediate reversible binding to phospholipid membranes. This property supports the role of synucleins in vesicular release at presynaptic nerve terminals (1-4). Although their normal cellular functions have not been clearly defined, synucleins have attracted considerable attention due to their involvement in neurodegenerative diseases. ·-synuclein is the major component of Lewy bodies in Parkinson's disease and has also been identified as the non-amyloid component of amyloid deposition, the hallmark of Alzheimer's disease (5,6). ß-and Á-synuclein are assumed to have a neuroprotective role by inhibiting ·-synuclein aggregation and toxicity (7,8).Synuclein expression is usually highly tissue-specific, and restricted to brain tissue and presynaptic terminals. However, a...

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Section: Introductionsupporting

confidence: 65%

Expression of α-, β- and γ-synuclein in colorectal cancer, and potential clinical significance in progression of the disease

Wang²,

Peng³

et al. 2009

Oncol Rep

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“…They are a natively unfolded group of proteins that are characterized by 5-6 repeats of the amino acid motif (KTKEGV), constituting most of the N-terminal half of the proteins [1][2][3] . The synucleins…”

Section: Introductionmentioning

confidence: 99%

Expression of γ-synuclein in colorectal cancer tissues and its role on colorectal cancer cell line HCT116

Feng²,

Peng³

et al. 2009

WJG

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Author contributions: Ye Q designed and performed the research, including performance of colony formation assay, cell migration and invasion assay and writing the paper; Feng B participated in designing the research and carried out immunohistochemistry; Peng YF performed isolation of RNA and protein, and carried out western blotting and CCK8 assay; Chen XH cultured cells, and carried out selection of stable transfectants; Cai Q carried out real-time quantitative RT-PCR; Yu BQ carried out plasmid construction; Li LH and Qiu MY collected tissue samples and clinicopathological data used in the study; Liu BY contributed vital reagents and analytical tools; Zheng MH took responsibility for financial support, and obtaining permission from all coauthors for the submission of any version of the paper and for any changes in authorship. RESULTS:The expression of γ-synuclein mRNA and protein was much higher in CRC tissue samples than in NNAT samples (P = 0.02, P = 0.036). There was a significant correlation between the γ-synuclein protein expression and clinical stage and lymph node involvement of CRC (P = 0.02, P = 0.033). In functional analysis we found that down-regulation of γ-synuclein expression in HCT116 cells could inhibit the growth, colony formation rate, and migration and invasion ability of HCT116 cells. CONCLUSION:Increased expression of γ-synuclein in CRC tissues and the biological effects of reduced γ-synuclein expression on HCT116 cells suggest that γ-synuclein may play a positive role in the progression of CRC.

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“…The normal expression of SNCG is restricted to the brain and periphery neuronal tissues (Lavedan et al, 1998) and its aberrant expression outside neuronal system is highly associated with human malignancies (Ji et al, 1997;Bruening et al, 2000;Wu et al, 2003;Yanagawa et al, 2004;Cao et al, 2005). SNCG expression has been detected in nine different types of human cancers including lung cancer.…”

Section: Introductionmentioning

confidence: 99%

Cigarette smoke induces demethylation of prometastatic oncogene synuclein-γ in lung cancer cells by downregulation of DNMT3B

et al. 2007

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The prometastatic oncogene synuclein-c (SNCG) is not expressed in normal lung tissues, but it is highly expressed in lung tumors. Here, we show that cigarette smoke extract (CSE) has strong inducing effects on SNCG gene expression in A549 lung cancer cells through demethylation of SNCG CpG island. CSE treatment also augments the invasive capacity of A549 cells in an SNCG-dependent manner. To elucidate the mechanisms underlying the demethylating effects of CSE, we examined expression levels of DNA methyltransferases (DNMTs), 1, 3A and 3B in CSE-treated cells. We show that the mRNA expression of DNMT3B is specifically downregulated by CSE with a kinetics concurrent to SNCG reexpression. Utilizing siRNA to knockdown DNMT3B expression, we show that inhibition of DNMT3B directly increases SNCG mRNA expression. We further show that exogenous overexpression of DNMT3B in an SNCG-positive lung cancer cell line H292 suppresses SNCG mRNA and protein expression and induces de novo methylation of SNCG CpG island, whereas overexpression of DNMT1 or DNMT3A has no effects. Taken together, these new findings demonstrate that tobacco exposure induces the abnormal expression of SNCG in lung cancer cells through downregulation of DNMT3B. This work sheds light on the molecular understanding of demethylation of this oncogene during cancer progression.

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Identification, localization and characterization of the human γ-synuclein gene

Cited by 171 publications

References 24 publications

Expression of α-, β- and γ-synuclein in colorectal cancer, and potential clinical significance in progression of the disease

Expression of α-, β- and γ-synuclein in colorectal cancer, and potential clinical significance in progression of the disease

Expression of γ-synuclein in colorectal cancer tissues and its role on colorectal cancer cell line HCT116

Cigarette smoke induces demethylation of prometastatic oncogene synuclein-γ in lung cancer cells by downregulation of DNMT3B

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