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241.
Hiroaki Fujita Simin Rahighi Mariko Akita Ryuichi Kato Yoshiteru Sasaki Soichi Wakatsuki Kazuhiro Iwai 《Molecular and cellular biology》2014,34(7):1322-1335
The linear ubiquitin chain assembly complex (LUBAC) ligase, consisting of HOIL-1L, HOIP, and SHARPIN, specifically generates linear polyubiquitin chains. LUBAC-mediated linear polyubiquitination has been implicated in NF-κB activation. NEMO, a component of the IκB kinase (IKK) complex, is a substrate of LUBAC, but the precise molecular mechanism underlying linear chain-mediated NF-κB activation has not been fully elucidated. Here, we demonstrate that linearly polyubiquitinated NEMO activates IKK more potently than unanchored linear chains. In mutational analyses based on the crystal structure of the complex between the HOIP NZF1 and NEMO CC2-LZ domains, which are involved in the HOIP-NEMO interaction, NEMO mutations that impaired linear ubiquitin recognition activity and prevented recognition by LUBAC synergistically suppressed signal-induced NF-κB activation. HOIP NZF1 bound to NEMO and ubiquitin simultaneously, and HOIP NZF1 mutants defective in interaction with either NEMO or ubiquitin could not restore signal-induced NF-κB activation. Furthermore, linear chain-mediated activation of IKK2 involved homotypic interaction of the IKK2 kinase domain. Collectively, these results demonstrate that linear polyubiquitination of NEMO plays crucial roles in IKK activation and that this modification involves the HOIP NZF1 domain and recognition of NEMO-conjugated linear ubiquitin chains by NEMO on another IKK complex. 相似文献
242.
Inhibition of poly(ADP-ribose) polymerase activity by Bcl-2 in association with the ribosomal protein S3a. 总被引:3,自引:0,他引:3
We screened a human lymphocyte cDNA library using the yeast two-hybrid system and an automodification domain of PARP as a probe. The DNA sequence of an isolated clone (clone 3-9) was identical to the partial cDNA sequence of the human ribosomal protein S3a. We confirmed that PARP interacts with clone 3-9 by performing binding studies using a GST-3-9 fusion protein as bait. We also demonstrated that native S3a in nuclear extracts of HL-60 cells interacts with the automodification domain of PARP and that PARP from nuclear extracts is coprecipitated with the GST-3-9 fusion protein. Furthermore, we demonstrated that Bcl-2 interacts with PARP in association with S3a and that the interaction of S3a and Bcl-2 with PARP causes a significant decrease in PARP activity. Since Bcl-2 failed to inhibit PARP activity in the absence of S3a, we suggest that Bcl-2 together with S3a prevents apoptosis probably by inhibiting PARP activity. 相似文献
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定量认识和理解气候与流域特征变化对淮河流域地表水文过程的影响,可以为科学管理淮河流域水资源提供重要的理论参考和技术支撑。评估了多控制因子联立求解归因方法的适用性,以此量化了淮河流域气候和Budyko参数n对不同年代蒸散发(ET)、径流变化(较基准期1961—1980年)的贡献,并且进行了归因分析,结果表明:1)多控制因子联立求解法可以准确有效地分离气候和参数n对ET和径流变化的贡献。2)在气候和参数n变化的共同影响下,20世纪80年代、90年代的ET和径流在沂沭泗河各水文分区均呈减小趋势,而在上游和中游各水文分区的变化则表现出明显的时空差异性。3)就各年代控制ET变化的主要因子,多数水文分区为参数n,其次为降水和潜在蒸散发(PET),分别集中在沂沭泗河地区和淮河上游。20世纪80年代,中游水文分区径流变化的主控因子为PET,其他水文分区则多为降水;而20世纪90年代和21世纪初多数水文分区的主控因子为参数n,其次为降水。总之,控制淮河流域ET和径流变化的物理机制具有明显的空间差异和年代际变化特征。 相似文献
246.
Akio Ueno Satoru Shimizu Shuji Tamamura Takeshi Naganuma Yasushi Ohmi Katsuhiko Kaneko 《Geomicrobiology journal》2014,31(8):654-663
Bacterial utilization of humic acids (HAs) was examined under aerobic conditions using Pseudomonas spp. from diatomite from a depth of 250 m below ground level in the Horonobe Underground Research Laboratory. HA decolorization and bacterial aggregation were observed during cultivation when an auxiliary carbon source was added. High-performance size-exclusion chromatography showed that high-molecular-weight HAs were produced. Fourier transform infrared spectroscopy indicated that carboxyl groups and polysaccharide-related substances in HAs were eliminated, while aliphatic structural units and amide groups were added to HAs. These results suggested that Pseudomonas spp. utilize and alter the molecular structure of HAs under aerobic conditions caused by the construction of underground facilities. 相似文献
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Summary The nucleotide sequence of a 2.5 kb region encompassing a curved DNA segment (BENT-9) randomly cloned from the total Escherichia coli chromosome was determined. This region was found to contain the dnaY gene encoding a transfer RNA. The curved DNA structure was demonstrated to be located just upstream of the dnaY promoter. The results of sequencing further revealed that the int gene of a cryptic prophage, qsr, which has been shown to be present in the E. coli genome, is located next to the dnaY gene. 相似文献
250.
The role of protein kinase C activation in a coupling of Ca2+-mobilizing receptors/GTP-binding protein/phospholipase C was examined using Xenopus oocytes before and after microinjection of mRNA purified from rat brains. Under voltage-clamp conditions, although the phorbol ester TPA per se never elicited any changes in ionic conductance, chloride current responses of mRNA-injected cells to 5-hydroxytryptamine and acetylcholine (ACh) were suppressed by an 8-min pretreatment of 12-O-tetradecanoyl-4 beta-phorbol-13-acetate (TPA), at nanomolar concentrations. Native ACh response in intact follicular oocytes was also inhibited by the TPA treatment. However, similar current responses triggered by the direct activation of their intracellular signalling pathway with guanosine-5'-O-(3-thio)triphosphate or Ca2+ were not affected by TPA. Biochemical analyses indicated that phosphorylation of 33,000- and 45,000-dalton proteins was markedly enhanced by TPA in vivo, and that stimulation of receptors with agonists as well as TPA treatment increased phosphoproteins in the membrane fraction of mRNA-injected oocytes. These observations suggest that protein kinase C may switch off the signal transduction from receptors to GTP-binding proteins and may participate in the negative feedback modulation of receptor-operated ion channel responses. 相似文献