FasL associated factors and their potential role in the regulation of FasL expression
3
Citation
36
Reference
10
Related Paper
Citation Trend
Abstract:
Fas Ligand (FasL) is a death factor with multiple functions. The expression and release of FasL is tightly regulated at a post-transcriptional level by sorting of FasL in so-called secretory lysosomes or directly on the cell membrane. The underlying mechanism and protein-protein interactions involved are largely unknown. Three putatively ‘FasL associated factors’ (FLAF1-3) had been identified earlier in a yeast two-hybrid screen by using the cytoplasmic portion of FasL as bait. Until today, nothing is known about their role in the context of FasL expression and function. Here we show that FLAFs interact with FasL via SH3 or WW domain binding to the proline-rich domain in the cytosolic tail of FasL. FLAF1 forms part of the formin binding protein 11 (FBP11, also called huntingtin-interacting protein A, HYPA), FLAF2 is part of the c-Cbl-associated protein SH3P12 = “sorbin and SH3 domain containing 1” and FLAF3 represents a portion of the BAI1-associated protein 2 (BAP2β). SH3P12 and BAP2β could precipitate FasL in double transfectants. The interaction of SH3P12/FasL and BAP2β/FasL results in the enhanced surface expression of FasL. These findings suggest that in contrast to other FasL interacting proteins, SH3P12 and BAP2β do not target FasL to the lysosomal compartment but rather might be involved in its surface expression.Keywords:
Fas ligand
研究背景： Fas 與 Fas Ligand (FasL) 是細胞凋亡的重要調控因子，免疫系統藉由細胞凋亡來維持體內細胞正常與平衡；癌症的發生與細胞逃避免疫監控，抑制細胞凋亡作用關係密切。目前已知有些腫瘤細胞會大量表現FasL，進而與免疫細胞的Fas結合，促使免疫細胞凋亡，使得癌症得以形成。已知Fas -670A/G 與 FasL -844C/T基因多型性與蛋白質表現量有關，但與口腔癌的相關研究並不多，因此我們想探討 Fas -670A/G 與 FasL -844C/T 基因多型性與口腔癌的相關性。
研究方法：口腔鱗狀上皮細胞癌（OSCC）的患者經由高醫口腔外科與病理切片確認診斷後，邀請這些患者參加調查，經簽署人體試驗同意書後，抽取血液萃取 DNA 與完成問卷調查獲得相關資料；對照組則是高雄縣某社區居民在健康檢查後經口腔檢查，無任何明顯口腔病變、組織發炎且無任何慢性疾病的人，以同樣的問題與樣本收集方式來進行收集。針對Fas-670A/G 與 FasL-844C/T 二個位置的基因多型性進行 PCR-RFLP 實驗，實驗結果以統計方法分析其相關性。
結果： Fas 與FasL 基因多型性分佈頻率在二組研究對象中並沒有顯著不同，在OSCC患者有較高比例的人有抽菸、喝酒、嚼食檳榔的習慣。Fas -670A/G和FasL -844 C/T基因多型性在OSCC與對照組間的頻率分佈並未達到統計上顯著相關。當進行物質使用習慣的分層分析，Fas -670A/G 與FasL-844C/T 基因多型性與OSCC的相關性仍然未達統計上顯著相關，但可以觀察到抽菸習慣對OSCC的危險比（OR）在研究對象攜帶Fas -670G/G 基因型時是8.68（95% CI＝1.26∼67.16）；攜帶 -670A/G基因型時OR值是3.43（95%CI＝1.48∼7.71），但攜帶 -670A/A基因型時OR值是6.39, 95%CI＝2.21∼18.33）。然而嚼食檳榔習慣對OSCC的OR值，在研究對象攜帶Fas -670G/G 基因型時是37.25（95%CI＝6.72∼317.48）；攜帶-670A/G 基因型OR值是19.27（95%CI＝8.41∼47.61），攜帶-670A/A基因型時OR值是8.60 （95%CI＝2.83∼27.09）。抽菸習慣對OSCC的OR值在研究對象攜帶FasL -844CT基因型時是3.40（95%CI＝1.17∼9.53），但在攜帶-844C/C基因型時OR值是5.91（95%CI＝2.68∼12.91）。嚼食檳榔習慣對OSCC的OR值，在研究對象攜帶FasL -844C/T基因型時是21.80 （95%CI＝8.50∼61.45），研究對象攜帶-844C/C基因型時OR值是12.45（95%CI＝5.28∼31.04），但在飲酒習慣則未達到統計上顯著。
結論： 研究結果發現 Fas -670A/G 與 FasL -844C/T基因多型性與口腔鱗狀上皮細胞癌沒有達統計上相關性。菸、酒、檳榔是口腔癌重要的危險因子，同時菸、酒、檳榔的使用習慣對OSCC的危險性，會受到Fas 基因在-670位置與FasL基因在-844C/T位置的基因多型性的影響，未來可能提供抽菸與嚼食檳榔在致癌化過程的不同思考方向。
Fas ligand
Cite
Citations (0)
In a soil bioassay, adult Deroceras reticulatum (Stylommatophora: Limacidae) and three different weight-classes of young Arion lusitanicus (Stylommatophora: Arionidae) were exposed to a single dosage (170 dauer larvae per g of soil) of the nematode Phasmarhabditis hermaphrodita monoxenically associated with the bacterium Moraxella osloensis. Groups of 10 slugs were continuously exposed to nematodes for 4 days, and then transferred individually to Petri-dishes containing a disc of Chinese cabbage as food. Food consumption—measured by image analysis—and slug mortality were recorded daily for 10 days. Food consumption was inhibited in both slug species tested. D. reticulatum stopped feeding 6 days after the start of nematode treatment, while all A. lusitanicus continued to feed. However, in the three weight-classes of A. lusitanicus (0.15 g, 0.24 g, 0.45 g), food consumption was reduced by at least 50 %. The greatest reduction in feeding, nearly 90 %, was noted in the smallest A. lusitanicus. The nematodes successfully killed D. reticulatum but were less efficient at killing young A. lusitanicus. At the end of the experiment, mortality was highest in D. reticultatum (98 %) and the smallest weight-class of A. lusitanicus (47 %). There was almost no mortality in the largest weight-class of A. lusitanicus treated with nematodes. P. hermaphrodita associated with M. osloensis can thus be considered as a biological control agent for young stages of A. lusitanicus for its effect as a feeding inhibitor, rather than for its ability to kill the slugs.
Slug
Cite
Citations (41)
In response to DNA damage, p53 undergoes post-translational modifications (including acetylation) that are critical for its transcriptional activity. However, the mechanism by which p53 acetylation is regulated is still unclear. Here, we describe an essential role for HLA-B-associated transcript 3 (Bat3)/Scythe in controlling the acetylation of p53 required for DNA damage responses. Depletion of Bat3 from human and mouse cells markedly impairs p53-mediated transactivation of its target genes Puma and p21 . Although DNA damage-induced phosphorylation, stabilization, and nuclear accumulation of p53 are not significantly affected by Bat3 depletion, p53 acetylation is almost completely abolished. Bat3 forms a complex with p300, and an increased amount of Bat3 enhances the recruitment of p53 to p300 and facilitates subsequent p53 acetylation. In contrast, Bat3-depleted cells show reduced p53–p300 complex formation and decreased p53 acetylation. Furthermore, consistent with our in vitro findings, thymocytes from Bat3-deficient mice exhibit reduced induction of puma and p21, and are resistant to DNA damage-induced apoptosis in vivo. Our data indicate that Bat3 is a novel and essential regulator of p53-mediated responses to genotoxic stress, and that Bat3 controls DNA damage-induced acetylation of p53.
Cite
Citations (125)
In the present study, several multivariate analyses were carried out to assess the taxonomic relationships among European species of the genus Anthoxanthum. A total of 1787 Anthoxanthum specimens representing all European taxa were analyzed. Thirty macro-morphological (13 quantitative and 17 qualitative) and 29 micro-morphological (7 quantitative and 22 qualitative) characters were considered. First, resemblances between specimens were established independently for macro- and micro-morphological characters using Gower's similarity coefficient, and were represented by means of principal coordinates and cluster analyses. Subsequently, different multivariate analyses were applied to quantitative and qualitative macromorphological data to determine the most discriminant characters and the accuracy of the present taxonomic structure of the genus. Finally, dissimilarities among groups of individuals -species and populations- were estimated using the information radius measure and then represented in different dendrograms. Within annuals, Anthoxanthum gracile is clearly differentiated morphologically, yet no compelling morphological differentiation can be found between Anthoxanthum aristatum and Anthoxanthum ovatum. Moreover, the definition of subspecies in the annual taxa is not supported by our results. Then, within perennials, although the morphological relationships among Anthoxanthum amarum, Anthoxanthum odoratum and Anthoxanthum alpinum have also been resolved, further research is needed to assess the taxonomic position of the Macaronesian endemic Anthoxanthum maderense.
Dendrogram
Cite
Citations (28)
Cite
Citations (5)
Holcus lanatus
Cite
Citations (21)
HLA-B-associated transcript 3 (BAT3) was originally identified as one of the genes located within human major histocompatibility complex. It encodes a large proline-rich protein with unknown function. In this study, we found that a fragment of the BAT3 gene product interacts with a candidate tumor suppressor, DAN, in the yeast-based two-hybrid system. We cloned the full-length rat BAT3 cDNA from a fibroblast 3Y1 cDNA library. Our sequence analysis has demonstrated that rat BAT3 cDNA is 3617 nucleotides in length and encodes a full-length BAT3 (1098 amino acids) with an estimated molecular mass of 114,801 daltons, which displays an 87.4% identity with human BAT3. The deletion experiment revealed that the N-terminal region (amino acid residues 1-80) of DAN was required for the interaction with BAT3. Green fluorescent protein-tagged BAT3 was largely localized in the cytoplasm of COS cells. Northern hybridization showed that BAT3 mRNA was expressed in all the adult rat tissues examined but predominantly in testis. In addition, the level of BAT3 mRNA expression was more downregulated in some of the transformed cells, including v-mos- and v-Ha-ras-transformed 3Y1 cells, than in the parental cells.
Cite
Citations (21)
SUMMARY A hitherto unrecorded virus having flexible rod‐shaped particles about 740–760 × 13 nm was isolated from Anthoxanthum odoratwn L. It was transmitted by sap inoculation, but not by several species of insect, seed or soil to 18 species of Gramineae including wheat, oats and barley. In susceptible species the virus normally produced a mosaic mottling of the leaves which was sometimes followed by a necrotic streaking or striping.
Mosaic virus
Cite
Citations (6)
目的探讨 Fas/FasL基因转染联合顺铂对直肠癌细胞的杀伤作用.方法构建 pcDNA3.1-Fas/FasL真核表达载体,将人 Fas/FasL基因通过脂质体导入直肠癌 8348细胞中 ,并利用 RT-PCR方法检测直肠癌 8348细胞的 Fas/FasL基因 mRNA表达.用 MTT法分析顺铂对转染前后的 8348细胞抑制增殖和诱导凋亡的能力.结果 Fas/FasL基因转染可明显增强直肠癌 8348细胞的 Fas/FasL表达.分别加入不同浓度顺铂( 1、 5、 10、 20、 40 μ g/ml), Fas转染组 8348细胞抑制率分别为 47.2%、 51.8%、 57.2%、 65.4%、 71.0%;后者细胞抑制率分别为 29.6%、 33.0%、 37.8%、 41.4%、 47.0%,其差异有显著性意义( t=15.33,P< 0.01); FasL转染组 8348细胞抑制率分别为 11.0%、 25.4%、 31.2%、 37.8%、 42.4%;对照组 8348细胞抑制率分别为 26.1%、 34.4%、 37.6%、 42.9%、 53.2%,其差异有显著性意义 ( t= 4.43,P< 0.05).结论转染的 Fas/FasL基因可显著上调直肠癌 8348细胞的 Fas/FasL表达; Fas基因转染联合顺铂对直肠癌细胞有更强的杀伤作用; FasL基因转染可减弱顺铂对 8348细胞的细胞毒作用,因此为直肠癌的基因治疗和化疗提供了理论依据.
Fas ligand
Cite
Citations (0)
客观：在人的宫颈癌调查在船边交货和船边交货 ligand (FasL ) 和它的生物行为的表示之间的关系。方法: Immunohistochemisty 技术被用来在颈的癌，颈的 interaepithelial 瘤形成的 16 个案例，长期的子宫颈炎的 10 个案例和正常的 10 个案例的 47 种情况中检测船边交货和 FasL 的表示宫颈。TUNEL 技术被用来在颈的癌的 47 种情况中观察 apoptic 房间。回顾的学习被执行发现在船边交货和 FasL 和房间的表示之间的关系 apoptosis，临床的阶段，病理学的分类，淋巴节点转移，预后和年龄。结果：船边交货和 FasL 的表示在不同宫颈是显著地不同的(P 0.05 ) ；在不同病理学的分类的宫颈癌房间 apoptosis 显得否定关系(R_s=-0.35， P < 0.05 ) 。宫颈癌房间 apoptosis 显著地更高比那在 inFas 积极、 FasL 积极船边交货否定、 FasL 否定(P < 0.05 ) 。Byretrospective 调查，船边交货否定、 FasL 积极与有颈的癌的病人的差的预测有关(P < 0.05 ) 。结论：在宫颈癌的 apoptosis 的开发让一条支持的规定在船边交货和 FasL 表示工作。基因治疗罐头 alterapoptosis 反常，因此在癌的房间表示导致 apoptosis 船边交货和 FasL。船边交货或 FasLmay 在预示的描述作为一个标记被拿。
Fas ligand
Cite
Citations (0)