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31.
Clifford DL Folmes D Kent Arrell Jelena Zlatkovic-Lindor Almudena Martinez-Fernandez Carmen Perez-Terzic Timothy J Nelson Andre Terzic 《Cell cycle (Georgetown, Tex.)》2013,12(15):2355-2365
Nuclear reprogramming resets differentiated tissue to generate induced pluripotent stem (iPS) cells. While genomic attributes underlying reacquisition of the embryonic-like state have been delineated, less is known regarding the metabolic dynamics underscoring induction of pluripotency. Metabolomic profiling of fibroblasts vs. iPS cells demonstrated nuclear reprogramming-associated induction of glycolysis, realized through augmented utilization of glucose and accumulation of lactate. Real-time assessment unmasked downregulated mitochondrial reserve capacity and ATP turnover correlating with pluripotent induction. Reduction in oxygen consumption and acceleration of extracellular acidification rates represent high-throughput markers of the transition from oxidative to glycolytic metabolism, characterizing stemness acquisition. The bioenergetic transition was supported by proteome remodeling, whereby 441 proteins were altered between fibroblasts and derived iPS cells. Systems analysis revealed overrepresented canonical pathways and interactome-associated biological processes predicting differential metabolic behavior in response to reprogramming stimuli, including upregulation of glycolysis, purine, arginine, proline, ribonucleoside and ribonucleotide metabolism, and biopolymer and macromolecular catabolism, with concomitant downregulation of oxidative phosphorylation, phosphate metabolism regulation, and precursor biosynthesis processes, prioritizing the impact of energy metabolism within the hierarchy of nuclear reprogramming. Thus, metabolome and metaboproteome remodeling is integral for induction of pluripotency, expanding on the genetic and epigenetic requirements for cell fate manipulation. 相似文献
32.
Sequence, organization, and evolution of the A+T region of Drosophila melanogaster mitochondrial DNA 总被引:2,自引:0,他引:2
The long (4.6-kb) A+T region of Drosophila melanogaster mitochondrial DNA
has been cloned and sequenced. The A+T region is organized in two large
arrays of tandemly repeated DNA sequence elements, with nonrepetitive
intervening and flanking sequences comprising only 22% of its length. The
first repeat array consists of five repeats of 338-373 bp. The second
consists of four intact 464-bp repeats and a fifth partial repeat of 137
bp. Three DNA sequence elements are found to be highly conserved in D.
melanogaster and in several Drosophila species with short A+T regions.
These include a 300-bp DNA sequence element that overlaps the DNA
replication origin and two thymidylate stretches identified on opposite DNA
strands. We conclude that the length heterogeneity observed in the A+T
regulatory region in mitochondrial DNAs from the genus Drosophila results
from the expansion (and contraction) of the number of repeated DNA sequence
elements. We also propose that the 300-bp conserved DNA sequence element,
in conjunction with another primary sequence determinant, perhaps the
adjacent thymidylate stretch, functions in the regulation of mitochondrial
DNA replication.
相似文献
33.
34.
Selective neutrality of glucose-6-phosphate dehydrogenase allozymes in Escherichia coli 总被引:2,自引:0,他引:2
Six naturally occurring alleles representing four electromorphs of the
enzyme glucose-6-phosphate dehydrogenase were transferred by P1- mediated
transduction from natural isolates of Escherichia coli into the genetic
background of E. coli K12 and were studied in pairwise competition in
chemostats limited for glucose in order to estimate differences in growth
rate associated with the alleles. Although the level of resolution of such
experiments is a growth rate differential of approximately 0.002 h-1, no
significant differences among the strains were found. Studies of apparent
Km and Vmax in crude enzyme extracts of the strains also failed to reveal
any significant differences among the electromorphs. These results support
the view that the alleles are selectively neutral or nearly neutral under
these conditions.
相似文献
35.
36.
Chromosomal DNA from 23 closely related, pathogenic strains of Escherichia
coli was digested and probed for the insertion sequences IS1, IS2, IS4,
IS5, and IS30. Under the assumption that elements residing in DNA
restriction fragments of the same apparent length are identical by descent,
parsimony analysis of these characters yielded a unique phylogenetic tree.
This analysis not only distinguished among bacterial strains that were
otherwise identical in their biochemical characteristics and enzyme
electrophoretic mobilities, but certain aspects of the topology of the tree
were consistent across several unrelated insertion elements. The
distribution of IS elements was then reexamined in light of the inferred
phylogenetic relationships to investigate the biological properties of the
elements, such as rates of insertion and deletion, and to discover apparent
recombinational events. The analysis shows that the pattern of distribution
of insertion elements in the bacterial genome is sufficiently stable for
epidemiological studies. Although the rate of recombination by conjugation
has been postulated to be low, at least two such events appear to have
taken place.
相似文献
37.
EDC3 phosphorylation regulates growth and invasion through controlling P‐body formation and dynamics
Jeremiah J Bearss Sathish KR Padi Neha Singh Marina CardoVila Jin H Song Ghassan Mouneimne Nikita Fernandes Yang Li Matthew R Harter Jaime MC Gard Anne E Cress Wolfgang Peti Andrew DL Nelson J Ross Buchan Andrew S Kraft Koichi Okumura 《EMBO reports》2021,22(4)
Regulation of mRNA stability and translation plays a critical role in determining protein abundance within cells. Processing bodies (P‐bodies) are critical regulators of these processes. Here, we report that the Pim1 and 3 protein kinases bind to the P‐body protein enhancer of mRNA decapping 3 (EDC3) and phosphorylate EDC3 on serine (S)161, thereby modifying P‐body assembly. EDC3 phosphorylation is highly elevated in many tumor types, is reduced upon treatment of cells with kinase inhibitors, and blocks the localization of EDC3 to P‐bodies. Prostate cancer cells harboring an EDC3 S161A mutation show markedly decreased growth, migration, and invasion in tissue culture and in xenograft models. Consistent with these phenotypic changes, the expression of integrin β1 and α6 mRNA and protein is reduced in these mutated cells. These results demonstrate that EDC3 phosphorylation regulates multiple cancer‐relevant functions and suggest that modulation of P‐body activity may represent a new paradigm for cancer treatment. 相似文献
38.
A nuclear gene for higher level phylogenetics: phosphoenolpyruvate carboxykinase tracks mesozoic-age divergences within Lepidoptera (Insecta) 总被引:3,自引:0,他引:3
The sequence of phosphoenolpyruvate carboxykinase (PEPCK) has been
previously identified as a promising candidate for reconstructing
Mesozoic-age divergences (Friedlander, Regier, and Mitter 1992, 1994). To
test this hypothesis more rigorously, 597 nucleotides of aligned PEPCK
coding sequence (approximately 30% of the coding region) were generated
from 18 species representing Mesozoic-age lineages of moths (Insecta:
Lepidoptera) and outgroup taxa. Relationships among basal Lepidoptera are
well established by morphological analysis, providing a strong test for the
utility of a gene which has not previously been used in systematics.
Parsimony and other phylogenetic analyses were conducted on nucleotides by
codon positions (nt1, nt2, nt3) separately and in combination, and on amino
acids, for comparison to the test phylogeny. The highest concordance was
achieved with nt1 + nt2, for which one of two most-parsimonious trees was
identical to the test phylogeny, and with all nucleotides when nt3 was
down-weighted sevenfold or higher, for which a single most-parsimonious
tree identical to the test phylogeny resulted. Substitutions in nt3
approached saturation in many, but not all, pairwise comparisons and their
exclusion or severe downweighting greatly increased the degree of
concordance with the test phylogeny. Neighbor-joining analysis confirms
this finding. The utility of PEPCK for phylogenetics is demonstrated over a
time span for which few other suitable genes are currently available.
相似文献
39.
Yoshito Nagano Toru Fukushima Kazuo Okemoto Keiichiro Tanaka David DL Bowtell Ze'ev A Ronai John C Reed Shu-ichi Matsuzawa 《Cell cycle (Georgetown, Tex.)》2011,10(15):2592-2602
p27kip1 has been implicated in cell cycle regulation, functioning as an inhibitor of cyclin-dependent kinase activity. In addition, p27 was also shown to affect cell migration, with accumulation of cytoplasmic p27 associated with tumor invasiveness. However, the mechanism underlying p27 regulation as a cytoplasmic protein is poorly understood. Here we show that glucose starvation induces proteasome-dependent degradation of cytoplasmic p27, accompanied by a decrease in cell motility. We also show that the glucose limitation-induced p27 degradation is regulated through an ubiquitin E3 ligase complex involving Siah1 and SIP/CacyBP. SIP−/− embryonic fibroblasts have increased levels of cytosolic p27 and exhibit increased cell motility compared with wild-type cells. These observations suggest that the Siah1/SIP E3 ligase complex regulates cell motility through degradation of p27.Key words: p27kip1, Siah1, SIP, glucose starvation, cell migration 相似文献
40.
The impact of gender and/or hormone variations on a wide variety of neural functions makes the choice between studying males or females (or both) of a given species difficult. Although female rats are widely used experimentally, few studies control for the stage of estrus. More detailed information about how to distinguish the various stages of the estrous cycle is needed. For the present study, vaginal smears were obtained once a day and stained using an adaptation of the Papanicolaou (PAP) procedure. Images are provided of unstained “wet” samples and the corresponding PAP stained smears illustrating the cellular profile for each stage of the cycle as well as post-ovariectomy. The different cell populations across the cycle were quantified and ratios determined to show trends between the predominant and other cell types in each stage of the estrous cycle. Both stained and unstained images and cell quantification data provide valuable guidelines for distinguishing the stages of the estrous cycle. 相似文献