1.
Mechanistic insights into metal ion activation and operator recognition by the ferric uptake regulator.
Deng, Z, Wang, Q, Liu, Z, Zhang, M, Machado, AC, Chiu, TP, Feng, C, Zhang, Q, Yu, L, Qi, L, et al
Nature communications. 2015;:7642
Abstract
Ferric uptake regulator (Fur) plays a key role in the iron homeostasis of prokaryotes, such as bacterial pathogens, but the molecular mechanisms and structural basis of Fur-DNA binding remain incompletely understood. Here, we report high-resolution structures of Magnetospirillum gryphiswaldense MSR-1 Fur in four different states: apo-Fur, holo-Fur, the Fur-feoAB1 operator complex and the Fur-Pseudomonas aeruginosa Fur box complex. Apo-Fur is a transition metal ion-independent dimer whose binding induces profound conformational changes and confers DNA-binding ability. Structural characterization, mutagenesis, biochemistry and in vivo data reveal that Fur recognizes DNA by using a combination of base readout through direct contacts in the major groove and shape readout through recognition of the minor-groove electrostatic potential by lysine. The resulting conformational plasticity enables Fur binding to diverse substrates. Our results provide insights into metal ion activation and substrate recognition by Fur that suggest pathways to engineer magnetotactic bacteria and antipathogenic drugs.
2.
Association of X-ray repair cross-complementing group 1 Arg194Trp, Arg399Gln and Arg280His polymorphisms with head and neck cancer susceptibility: a meta-analysis.
Wu, W, Liu, L, Yin, Z, Guan, P, Li, X, Zhou, B
PloS one. 2014;(1):e86798
Abstract
BACKGROUND Previous studies on the association of X-ray repair cross-complementing group 1 (XRCC1) Arg194Trp, Arg399Gln, and Arg280His polymorphisms with head and neck cancer (HNC) have produced inconsistent results. The aim of the present study was to evaluate the effects of these three polymorphic variants on HNC risk. METHODS The PubMed and EMBASE databases were searched for genetic association studies on the XRCC1 Arg194Trp, Arg399Gln, and Arg280His polymorphisms and HNC risk. (The most recent search was conducted on 20 August, 2013.) Twenty-six studies were identified and meta-analysis was performed to evaluate the association between the polymorphism and HNC by calculating combined odds ratios and 95% confidence intervals. RESULTS No significant association was found under the allelic, homozygous, heterozygote, and dominant genetic models in the overall comparison. Further, no significant association between the XRCC1 Arg399Gln and Arg280His polymorphisms and HNC risk was detected under the four genetic models in subgroup analyses based on ethnicity, cancer site, and whether or not the studies had been adjusted for cigarette smoking and alcohol. However, in stratified analyses based on cancer site, a significant association was found between the XRCC1 Arg194Trp polymorphism and oral cancer under the allelic, heterozygote, and dominant models. The XRCC1 Arg194Trp polymorphism was significantly associated with HNC risk in studies that were adjusted for smoking and alcohol under the homozygous and heterozygote models. CONCLUSION The meta-analysis results suggest that the XRCC1 Arg399Gln and Arg280His polymorphisms are probably not associated with the risk of HNC, but the XRCC1 Arg194Trp polymorphism was associated with increased risk of HNC in the subgroup analysis of studies adjusted for smoking and alcohol and with increased risk of oral cancer in the stratified analyses based on cancer site. Further studies with larger samples are needed to confirm these findings.
3.
[Ovarian carcinoma cell inhibits T cell JAK-STAT signal transduction pathway, an experimental study].
Wang, H, Xie, X, Lü, WG, Ye, DF, Chen, HZ, Li, X, Cheng, Q
Zhonghua yi xue za zhi. 2003;(11):972-5
Abstract
OBJECTIVE To investigate the effect of ovarian carcinoma cell on T cell JAK-STAT signal transduction pathway and its role in the ovarian carcinoma induced immunosupression. METHODS Human ovarian carcinoma cells of OVCAR3. CAOV3, and SKOV3 lines were cultured. CD8(+) T cells were isolated from the peripheral venous blood of healthy persons. Then the supernatants of these ovarian carcinoma cell lines and RPMI-1640 were added into the culture of CD8(+) T cells (groups I, II, III, and control). Thiazolyl blue (MTT) method was used to detect the growth of CD8(+) T cell. The cell cycle was examined by flow cytometry. The secretion of the Tc1 type cytokine interferon (IFN)-gamma mRNA and the secretion of the Tc2 type cytokine interleukin (IL)-10 mRNA were detected by RT-PCR. The expression of signaling molecules JAK and JAK3 and the phosphorylated activation of STAT3 and STAT5 in the CD8(+) T cell were analyzed by Western blotting. RESULTS The absorbance at the wavelength 570 nm of CD8(+) T cell culture was 0.23 +/- 0.03, 0.28 +/- 0.06, and 0.29 +/- 0.05 in the group I, II, and III, all significantly lower than that in the group IV (0.79 +/- 0.07, all P < 0.01). The percentages of CD8(+) T cells at the stage S and stage G(2)/M were lower, and those in stage G(1)/G(0) were higher in groups I, II, and III than in group IV (all P < 0.01). The IFN-gamma expression was significantly lower in groups I, II, and III in comparison with that in group IV. However, the expression of IL-10 was significantly higher in groups I, II, and III in comparison with that in group IV. The expression of JAK3 protein, but not JAK1 protein, was significantly lower in groups I, II, and III in comparison with that in group IV. The phosphorylated activation of STAT5 was suppressed significantly in groups I, II, and III, whereas the phosphorylated activation of STAT3 was suppressed only in group I. CONCLUSION Ovarian carcinoma may suppress T cell proliferation through inhibition of the JAK-STAT signal transduction pathway, which may be a mechanism of ovarian carcinoma induced immunosuppression.