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121.
Phosphorylation on tyrosine-15 of p34(Cdc2) by ErbB2 inhibits p34(Cdc2) activation and is involved in resistance to taxol-induced apoptosis 总被引:4,自引:0,他引:4
Tan M Jing T Lan KH Neal CL Li P Lee S Fang D Nagata Y Liu J Arlinghaus R Hung MC Yu D 《Molecular cell》2002,9(5):993-1004
ErbB2 overexpression confers resistance to taxol-induced apoptosis by inhibiting p34(Cdc2) activation. One mechanism is via ErbB2-mediated upregulation of p21(Cip1), which inhibits Cdc2. Here, we report that the inhibitory phosphorylation on Cdc2 tyrosine (Y)15 (Cdc2-Y15-p) is elevated in ErbB2-overexpressing breast cancer cells and primary tumors. ErbB2 binds to and colocalizes with cyclin B-Cdc2 complexes and phosphorylates Cdc2-Y15. The ErbB2 kinase domain is sufficient to directly phosphorylate Cdc2-Y15. Increased Cdc2-Y15-p in ErbB2-overexpressing cells corresponds with delayed M phase entry. Expressing a nonphosphorylatable mutant of Cdc2 renders cells more sensitive to taxol-induced apoptosis. Thus, ErbB2 membrane RTK can confer resistance to taxol-induced apoptosis by directly phosphorylating Cdc2. 相似文献
122.
SPOP Promotes Nanog Destruction to Suppress Stem Cell Traits and Prostate Cancer Progression 总被引:1,自引:0,他引:1
123.
Sara Bobone Gianfranco Bocchinfuso Yoonkyung Park Antonio Palleschi Kyung‐Soo Hahm Lorenzo Stella 《Journal of peptide science》2013,19(12):758-769
Antimicrobial peptides (AMPs) are promising compounds for developing new antibiotic drugs against drug‐resistant bacteria. Many of them kill bacteria by perturbing their membranes but exhibit no significant toxicity towards eukaryotic cells. The identification of the features responsible for this selectivity is essential for their pharmacological development. AMPs exhibit few conserved features, but a statistical analysis of an AMP sequence database indicated that many α‐helical AMPs surprisingly have a helix‐breaking Pro residue in the middle of their sequence. To discriminate among the different possible hypotheses for the functional role of this feature, we designed an analogue of the antimicrobial peptide P5, in which the central Pro was deleted (analogue P5Del). Pro removal resulted in a dramatic increase of toxicity. This was explained by the observation that P5Del binds both charged and neutral membranes, whereas P5 has no appreciable affinity towards neutral bilayers. CD and simulative data provided a rationalization of this behavior. In solution P5, due to the presence of Pro, attains compact conformations, in which its apolar residues are partially shielded from the solvent, whereas P5Del is more helical. These structural differences reduce the hydrophobic driving force for association of P5 to neutral membranes, whereas its binding to anionic bilayers can still take place because of electrostatic attraction. After membrane binding, the Pro residue does not preclude the attainment of a membrane‐active amphiphilic helical conformation. These findings shed light on the role of Pro residues in the selectivity of AMPs and provide hints for the design of new, highly selective compounds. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd. 相似文献
124.
Raisinghani M Zhong L Jeffry JA Bishnoi M Pabbidi RM Pimentel F Cao DS Evans MS Premkumar LS 《American journal of physiology. Cell physiology》2011,301(3):C587-C600
Transient receptor potential (TRP) ankyrin 1 (TRPA1) is a Ca(2+)-permeant, nonselective cationic channel. It is predominantly expressed in the C afferent sensory nerve fibers of trigeminal and dorsal root ganglion neurons and is highly coexpressed with the nociceptive ion channel transient receptor potential vanilloid 1 (TRPV1). Several physical and chemical stimuli have been shown to activate the channel. In this study, we have used electrophysiological techniques and behavioral models to characterize the properties of TRPA1. Whole cell TRPA1 currents induced by brief application of lower concentrations of N-methyl maleimide (NMM) or allyl isothiocyanate (AITC) can be reversed readily by washout, whereas continuous application of higher concentrations of NMM or AITC completely desensitized the currents. The deactivation and desensitization kinetics differed between NMM and AITC. TRPA1 current amplitude increased with repeated application of lower concentrations of AITC, whereas saturating concentrations of AITC induced tachyphylaxis, which was more pronounced in the presence of extracellular Ca(2+). The outward rectification exhibited by native TRPA1-mediated whole cell and single-channel currents was minimal as compared with other TRP channels. TRPA1 currents were negatively modulated by protons and polyamines, both of which activate the heat-sensitive channel, TRPV1. Interestingly, neither protein kinase C nor protein kinase A activation sensitized AITC-induced currents, but each profoundly sensitized capsaicin-induced currents. Current-clamp experiments revealed that AITC produced a slow and sustained depolarization as compared with capsaicin. TRPA1 is also expressed at the central terminals of nociceptors at the caudal spinal trigeminal nucleus. Activation of TRPA1 in this area increases the frequency and amplitude of miniature excitatory or inhibitory postsynaptic currents. In behavioral studies, intraplantar and intrathecal administration of AITC induced more pronounced and prolonged changes in nociceptive behavior than those induced by capsaicin. In conclusion, the characteristics of TRPA1 we have delineated suggest that it might play a unique role in nociception. 相似文献
125.
HANS‐PETER SCHULTZE DIRK FUCHS SAMUEL GIERSCH CHRISTINA IFRIM WOLFGANG STINNESBECK 《Palaeontology》2010,53(3):689-694
Abstract: The supposed vestige of a cephalopod gladius from Turonian platy limestones at Vallecillo, north‐east Mexico, named Palaeoctopus pelagicus by Fuchs et al. in 2008, is reinterpreted and shown to be a gular plate of a coelacanth fish, possibly of the genus Megacoelacanthus. In addition to the gular plate, two extrascapulars and fin rays of all fins are preserved on one slab and its counterpart. This is the first record of a coelacanth from these lower Turonian strata at Vallecillo, which are rich in fish. 相似文献
126.
Shugeng Cao Brian T. Murphy Caleb Foster John S. Lazo David G.I. Kingston 《Bioorganic & medicinal chemistry》2009,17(6):2276-2281
Some simplified adociaquinone B analogs and a series of 1,4-naphthoquinone derivatives were synthesized and tested against the three enzymes Cdc25B, MKP-1, and MKP-3. Cdc25B and MKP-1 in particular are enzymes overexpressed in human cancer cells, and they represent potential molecular targets for novel cancer chemotherapeutic treatments. A number of analogs exhibited significant inhibitory activity against these enzymes, and the bioassay data in addition to structure–activity relationships of these compounds will be discussed. 相似文献
127.
Plant strategy and life‐history theories make different predictions about reproductive efficiency under competition. While strategy theory suggests under intense competition iteroparous perennial plants delay reproduction and semelparous annuals reproduce quickly, life‐history theory predicts both annual and perennial plants increase resource allocation to reproduction under intense competition. We tested (1) how simulated competition influences reproductive efficiency and competitive ability (CA) of different plant life histories and growth forms; (2) whether life history or growth form is associated with CA; (3) whether shade avoidance plasticity is connected to reproductive efficiency under simulated competition. We examined plastic responses of 11 herbaceous species representing different life histories and growth forms to simulated competition (spectral shade). We found that both annual and perennial plants invested more to reproduction under simulated competition in accordance with life‐history theory predictions. There was no significant difference between competitive abilities of different life histories, but across growth forms, erect species expressed greater CA (in terms of leaf number) than other growth forms. We also found that shade avoidance plasticity can increase the reproductive efficiency by capitalizing on the early life resource acquisition and conversion of these resources into reproduction. Therefore, we suggest that a reassessment of the interpretation of shade avoidance plasticity is necessary by revealing its role in reproduction, not only in competition of plants. 相似文献
128.
Due to resource scarcity and environmental degradation, a new development concept emphasizing environmental concerns, called the circular economy (CE), has been enacted in legislation in China. This environmental management concept can be implemented at three levels, namely, region, industrial zone, and individual enterprise, with the objective of boosting economic development while lessening environmental and resource challenges. Environmental supply chain cooperation (ESCC), an approach that utilizes customer and supplier cooperation in environmental management, has been initiated among Chinese enterprises. Using survey data collected from 396 Chinese manufacturers, we examine the role of ESCC practices in influencing the relationship between implementing CE practices and the achievement of performance outcomes by testing the moderation and mediation effects of ESCC practices on the CE practice‐performance relationship through hierarchical regression analysis. Our data analyses indicate that ESCC practices are useful by moderation and, in some cases, essential by mediation, for Chinese manufacturers seeking to realize the performance targets desired in CE practices. The results highlight the need for Chinese manufacturers to improve supply chain coordination in their implementation of CE. On the policy side, our research findings suggest that ESCC practices are beneficial and, in some cases, necessary for the development of CE in China. 相似文献
129.
Norah E. M. Brown Marco Milazzo Samuel P. S. Rastrick Jason M. Hall‐Spencer Thomas W. Therriault Christopher D. G. Harley 《Global Change Biology》2018,24(1):e112-e127
Ocean acidification may have far‐reaching consequences for marine community and ecosystem dynamics, but its full impacts remain poorly understood due to the difficulty of manipulating pCO2 at the ecosystem level to mimic realistic fluctuations that occur on a number of different timescales. It is especially unclear how quickly communities at various stages of development respond to intermediate‐scale pCO2 change and, if high pCO2 is relieved mid‐succession, whether past acidification effects persist, are reversed by alleviation of pCO2 stress, or are worsened by departures from prior high pCO2 conditions to which organisms had acclimatized. Here, we used reciprocal transplant experiments along a shallow water volcanic pCO2 gradient to assess the importance of the timing and duration of high pCO2 exposure (i.e., discrete events at different stages of successional development vs. continuous exposure) on patterns of colonization and succession in a benthic fouling community. We show that succession at the acidified site was initially delayed (less community change by 8 weeks) but then caught up over the next 4 weeks. These changes in succession led to homogenization of communities maintained in or transplanted to acidified conditions, and altered community structure in ways that reflected both short‐ and longer‐term acidification history. These community shifts are likely a result of interspecific variability in response to increased pCO2 and changes in species interactions. High pCO2 altered biofilm development, allowing serpulids to do best at the acidified site by the end of the experiment, although early (pretransplant) negative effects of pCO2 on recruitment of these worms were still detectable. The ascidians Diplosoma sp. and Botryllus sp. settled later and were more tolerant to acidification. Overall, transient and persistent acidification‐driven changes in the biofouling community, via both past and more recent exposure, could have important implications for ecosystem function and food web dynamics. 相似文献
130.
延长光照时间对烟草叶片生长发育及光合特性的影响 总被引:5,自引:0,他引:5
以烤烟品种‘云烟87’为材料,采用夜间人工补光的方式,以自然光照时间为对照,设置增加1h、2h和3h光照3个处理,研究延长光照时间对烟草生长发育、叶绿素含量及光合作用、叶绿素荧光参数和光响应曲线的影响。结果表明:(1)与对照相比,延长光照时间2h处理下烟株叶长、叶宽、株高显著增加,1h、3h处理影响不显著。(2)延长光照处理显著降低比叶面积,提高叶片叶绿素a、b、叶绿素a+b、类胡萝卜素含量,但1h、3h处理的变化幅度小于2h处理。(3)延长光照时间1h和2h处理下叶片净光合速率(Pn)、气孔导度(Gs)、胞间CO2浓度(Ci)显著升高,3h处理影响不大;延长光照处理显著提高了PSⅡ最大光化学量子效率(Fv/Fm)、PSⅡ实际光化学量子效率(ΦPSⅡ)、光化学淬灭系数(qP),降低了非光化学淬灭系数(NPQ),其中2h处理影响幅度最大,但对初始荧光强度F0影响不显著;延长光照处理下烟草叶片的最大净光合速率(Pmax)和光饱和点(Isat)均升高,但光补偿点(Ic)没有明显的变化。研究表明,适当延长光照时间有利于叶片生长发育和干物质积累,提高叶绿素含量,促进光合作用,缓解光抑制现象,充分利用光能,提高叶片光合同化效率。 相似文献