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排序方式: 共有139条查询结果,搜索用时 15 毫秒
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Silvia Peppicelli Elena Andreucci Jessica Ruzzolini Anna Laurenzana Francesca Margheri Gabriella Fibbi Mario Del Rosso Francesca Bianchini Lido Calorini 《Cellular and molecular life sciences : CMLS》2017,74(15):2761-2771
Although surgical excision, chemo-, and radio-therapy are clearly advanced, tumors may relapse due to cells of the so-called “minimal residual disease”. Indeed, small clusters of tumor cells persist in host tissues after treatment of the primary tumor elaborating strategies to survive and escape from immunological attacks before their relapse: this variable period of remission is known as “cancer dormancy”. Therefore, it is crucial to understand and consider the major concepts addressing dormancy, to identify new targets and disclose potential clinical strategies. Here, we have particularly focused the relationships between tumor microenvironment and cancer dormancy, looking at a re-appreciated aspect of this compartment that is the low extracellular pH. Accumulating evidences indicate that acidity of tumor microenvironment is associated with a poor prognosis of tumor-bearing patients, stimulates a chemo- and radio-therapy resistant phenotype, and suppresses the tumoricidal activity of cytotoxic lymphocytes and natural killer cells, and all these aspects are useful for dormancy. Therefore, this review discusses the possibility that acidity of tumor microenvironment may provide a new, not previously suggested, adequate milieu for “dormancy” of tumor cells. 相似文献
84.
Hermann JC Marti-Arbona R Fedorov AA Fedorov E Almo SC Shoichet BK Raushel FM 《Nature》2007,448(7155):775-779
With many genomes sequenced, a pressing challenge in biology is predicting the function of the proteins that the genes encode. When proteins are unrelated to others of known activity, bioinformatics inference for function becomes problematic. It would thus be useful to interrogate protein structures for function directly. Here, we predict the function of an enzyme of unknown activity, Tm0936 from Thermotoga maritima, by docking high-energy intermediate forms of thousands of candidate metabolites. The docking hit list was dominated by adenine analogues, which appeared to undergo C6-deamination. Four of these, including 5-methylthioadenosine and S-adenosylhomocysteine (SAH), were tested as substrates, and three had substantial catalytic rate constants (10(5) M(-1 )s(-1)). The X-ray crystal structure of the complex between Tm0936 and the product resulting from the deamination of SAH, S-inosylhomocysteine, was determined, and it corresponded closely to the predicted structure. The deaminated products can be further metabolized by T. maritima in a previously uncharacterized SAH degradation pathway. Structure-based docking with high-energy forms of potential substrates may be a useful tool to annotate enzymes for function. 相似文献
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86.
Renna MD Oyadeyi AS Bossi E Kottra G Peres A 《Cellular and molecular life sciences : CMLS》2011,68(17):2961-2975
The functional and structural basis of reverse operation of PepT1 has been studied in Xenopus oocytes expressing the wild-type
and mutated forms of this protein. Using brief pulses from a negative holding potential, wild-type and Arg282 mutants exhibit
outward currents in the presence of Gly-Gln. The reversal potential of these currents is affected by both pH and substrate
concentration, confirming coupled transport in the wild type and in the mutants as well. Long-lasting voltage and current-clamp
experiments show that the outward currents are only temporary, and reflect accumulation and/or depletion effects near the
membrane. The ability to operate in reverse mode was confirmed in all isoforms by intracellular injection of substrate. The
role of Arg282 and Asp341 in the reverse transport was also investigated using charged substrates. Positive Lys-Gly (but not
Gly-Lys) showed enhanced transport currents in the Arg282 mutants. In contrast, negative Gly-Asp and Asp-Gly elicited modest
currents in all isoforms. 相似文献
87.
Shaw-Smith C Pittman AM Willatt L Martin H Rickman L Gribble S Curley R Cumming S Dunn C Kalaitzopoulos D Porter K Prigmore E Krepischi-Santos AC Varela MC Koiffmann CP Lees AJ Rosenberg C Firth HV de Silva R Carter NP 《Nature genetics》2006,38(9):1032-1037
Recently, the application of array-based comparative genomic hybridization (array CGH) has improved rates of detection of chromosomal imbalances in individuals with mental retardation and dysmorphic features. Here, we describe three individuals with learning disability and a heterozygous deletion at chromosome 17q21.3, detected in each case by array CGH. FISH analysis demonstrated that the deletions occurred as de novo events in each individual and were between 500 kb and 650 kb in size. A recently described 900-kb inversion that suppresses recombination between ancestral H1 and H2 haplotypes encompasses the deletion. We show that, in each trio, the parent of origin of the deleted chromosome 17 carries at least one H2 chromosome. This region of 17q21.3 shows complex genomic architecture with well-described low-copy repeats (LCRs). The orientation of LCRs flanking the deleted segment in inversion heterozygotes is likely to facilitate the generation of this microdeletion by means of non-allelic homologous recombination. 相似文献
88.
Proteoglycans (PGs), a family of complex post-translationally sculptured macromolecules, are fundamental regulators of most
normal and aberrant cellular functions. The unparalleled structural–functional diversity of PGs endows them with the ability
to serve as critical mediators of the tumor cells’ interaction with the host microenvironment, while directly contributing
to the organization and dynamic remodeling of this milieu. Despite their indisputable importance during embryonic development
and in the adult organism, and their frequent dysregulation in tumor lesions, their precise involvement in tumorigenesis awaits
a more decisive demonstration. Particularly challenging is to ascertain to what extent selected PGs may catalyze tumor progression
and to what extent they may inhibit it, implying antithetic functions of individual PGs. Integrated efforts are needed to
consolidate the routine use of PGs in the clinical monitoring of cancer patients and to broaden the exploitation of these
macromolecules as therapeutic targets. Several PGs have the required attributes to be contemplated as effective antigens for
immunotherapeutic approaches, while the tangible results obtained in recent clinical trials targeting the NG2/CSPG4 transmembrane
PG urge further development of PG-based cancer treatment modalities. 相似文献
89.
The nucleotide-binding proteins Nubp1 and Nubp2 are negative regulators of ciliogenesis 总被引:1,自引:1,他引:0
Elena Kypri Andri Christodoulou Giannis Maimaris Mette Lethan Maria Markaki Costas Lysandrou Carsten W. Lederer Nektarios Tavernarakis Stefan Geimer Lotte B. Pedersen Niovi Santama 《Cellular and molecular life sciences : CMLS》2014,71(3):517-538
Nucleotide-binding proteins Nubp1 and Nubp2 are MRP/MinD-type P-loop NTPases with sequence similarity to bacterial division site-determining proteins and are conserved, essential proteins throughout the Eukaryotes. They have been implicated, together with their interacting minus-end directed motor protein KIFC5A, in the regulation of centriole duplication in mammalian cells. Here we show that Nubp1 and Nubp2 are integral components of centrioles throughout the cell cycle, recruited independently of KIFC5A. We further demonstrate their localization at the basal body of the primary cilium in quiescent vertebrate cells or invertebrate sensory cilia, as well as in the motile cilia of mouse cells and in the flagella of Chlamydomonas. RNAi-mediated silencing of nubp-1 in C. elegans causes the formation of morphologically aberrant and additional cilia in sensory neurons. Correspondingly, downregulation of Nubp1 or Nubp2 in mouse quiescent NIH 3T3 cells markedly increases the number of ciliated cells, while knockdown of KIFC5A dramatically reduces ciliogenesis. Simultaneous double silencing of Nubp1 + KIFC5A restores the percentage of ciliated cells to control levels. We document the normal ciliary recruitment, during these silencing regimes, of basal body proteins critical for ciliogenesis, namely CP110, CEP290, cenexin, Chibby, AurA, Rab8, and BBS7. Interestingly, we uncover novel interactions of Nubp1 with several members of the CCT/TRiC molecular chaperone complex, which we find enriched at the basal body and recruited independently of the Nubps or KIFC5A. Our combined results for Nubp1, Nubp2, and KIFC5A and their striking effects on cilium formation suggest a central regulatory role for these proteins, likely involving CCT/TRiC chaperone activity, in ciliogenesis. 相似文献
90.
Abd El-Aziz MM Barragan I O'Driscoll CA Goodstadt L Prigmore E Borrego S Mena M Pieras JI El-Ashry MF Safieh LA Shah A Cheetham ME Carter NP Chakarova C Ponting CP Bhattacharya SS Antinolo G 《Nature genetics》2008,40(11):1285-1287
Using a positional cloning approach supported by comparative genomics, we have identified a previously unreported gene, EYS, at the RP25 locus on chromosome 6q12 commonly mutated in autosomal recessive retinitis pigmentosa. Spanning over 2 Mb, this is the largest eye-specific gene identified so far. EYS is independently disrupted in four other mammalian lineages, including that of rodents, but is well conserved from Drosophila to man and is likely to have a role in the modeling of retinal architecture. 相似文献