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161.
In the yeast Saccharomyces cerevisiae, the G protein beta gamma subunits are essential for pheromone signaling. The Galpha subunit Gpa1 can also promote signaling, but the effectors in this pathway are not well characterized. To identify candidate Gpa1 effectors, we expressed the constitutively active Gpa1(Q323L) mutant in each of nearly 5000 gene-deletion strains and measured mating-specific responses. Our analysis reveals a requirement for both the catalytic (Vps34) and regulatory (Vps15) subunits of the sole phosphatidylinositol 3-kinase in yeast. We demonstrate that Gpa1 is present at endosomes, where it interacts directly with both Vps34 and Vps15 and stimulates increased production of phosphatidylinositol 3-phosphate. Notably, Vps15 binds to GDP-bound Gpa1 and is predicted to have a seven-WD repeat structure similar to that of known G protein beta subunits. These findings reveal two new components of the pheromone signaling pathway. More remarkably, these proteins appear to comprise a preformed effector-G beta subunit assembly and function at the endosome rather than at the plasma membrane. 相似文献
162.
163.
Jihui Ren Coney Pei-Chen Lin Manish C. Pathak Brenda R. S. Temple Aaron H. Nile Carl J. Mousley Mara C. Duncan Debra M. Eckert Thomas J. Leiker Pavlina T. Ivanova David S. Myers Robert C. Murphy H. Alex Brown Jolien Verdaasdonk Kerry S. Bloom Eric A. Ortlund Aaron M. Neiman Vytas A. Bankaitis 《Molecular biology of the cell》2014,25(5):712-727
Lipid droplet (LD) utilization is an important cellular activity that regulates energy balance and release of lipid second messengers. Because fatty acids exhibit both beneficial and toxic properties, their release from LDs must be controlled. Here we demonstrate that yeast Sfh3, an unusual Sec14-like phosphatidylinositol transfer protein, is an LD-associated protein that inhibits lipid mobilization from these particles. We further document a complex biochemical diversification of LDs during sporulation in which Sfh3 and select other LD proteins redistribute into discrete LD subpopulations. The data show that Sfh3 modulates the efficiency with which a neutral lipid hydrolase-rich LD subclass is consumed during biogenesis of specialized membrane envelopes that package replicated haploid meiotic genomes. These results present novel insights into the interface between phosphoinositide signaling and developmental regulation of LD metabolism and unveil meiosis-specific aspects of Sfh3 (and phosphoinositide) biology that are invisible to contemporary haploid-centric cell biological, proteomic, and functional genomics approaches. 相似文献
164.
Yaoyu Chen Jinyun Chen Jianjun Yu Guizhi Yang Emilia Temple Fred Harbinski Hui Gao Christopher Wilson Raymond Pagliarini Wenlai Zhou 《The Journal of biological chemistry》2014,289(27):18914-18927
Heat shock protein 90 (HSP90) inhibition inhibits cancer cell proliferation through depleting client oncoproteins and shutting down multiple oncogenic pathways. Therefore, it is an attractive strategy for targeting human cancers. Several HSP90 inhibitors, including AUY922 and STA9090, show promising effects in clinical trials. However, the efficacy of HSP90 inhibitors may be limited by heat shock factor 1 (HSF1)-mediated feedback mechanisms. Here, we identify, through an siRNA screen, that the histone H3 lysine 4 methyltransferase MLL1 functions as a coactivator of HSF1 in response to HSP90 inhibition. MLL1 is recruited to the promoters of HSF1 target genes and regulates their expression in response to HSP90 inhibition. In addition, a striking combination effect is observed when MLL1 depletion is combined with HSP90 inhibition in various human cancer cell lines and tumor models. Thus, targeting MLL1 may block a HSF1-mediated feedback mechanism induced by HSP90 inhibition and provide a new avenue to enhance HSP90 inhibitor activity in human cancers. 相似文献
165.
In spite of the increasing application of DNA fingerprinting to natural
populations and to the genetic identification of humans, explicit methods
for estimation of basic population genetic parameters from DNA
fingerprinting data have not been developed. Contributing to this omission
is the inability to determine, for multilocus fingerprinting probes,
relatively important genetic information, such as the number of loci, the
number of alleles, and the distribution of these alleles into specific
loci. One of the most useful genetic parameters that could be derived from
such data would be the average heterozygosity, which has traditionally been
employed to measure the level of genetic variation within populations and
to compare genetic variation among different loci. We derive here explicit
formulas for both the estimation of average heterozygosity at multiple
hypervariable loci and a maximum value for this estimate. These estimates
are based upon the DNA restriction-pattern matrices that are typical for
fingerprinting studies of humans and natural populations. For several
empirical data sets from our laboratory, estimates of average and maximal
heterozygosity are shown to be relatively close to each other. Furthermore,
variances of these statistics based on simulation studies are relatively
small. These observations, as well as consideration of the effect of
missing alleles and alternate numbers of loci, suggest that the average
heterozygosity can be accurately estimated using phenotypic DNA fingerprint
patterns, because this parameter is relatively insensitive to the lack of
certain genetic information.
相似文献
166.
Human IL-3 (multi-CSF): identification by expression cloning of a novel hematopoietic growth factor related to murine IL-3 总被引:102,自引:0,他引:102
Y C Yang A B Ciarletta P A Temple M P Chung S Kovacic J S Witek-Giannotti A C Leary R Kriz R E Donahue G G Wong 《Cell》1986,47(1):3-10
A cDNA clone encoding a novel hematopoietic growth factor activity produced by a gibbon T cell line has been identified using a mammalian cell expression cloning system. The sequence of this cDNA proved to have significant homology to the sequence encoding murine interleukin 3 (IL-3). The human gene, which was readily identified because of its high degree of homology to the gibbon sequence, also displayed significant homology with the murine IL-3 sequence. The recombinant gibbon IL-3 protein proved to have multipotent colony stimulating activity when tested with normal human bone marrow cells, proving that this primate hematopoietin is not only structurally but also functionally related to murine IL-3. 相似文献
167.
168.
Britten CJ; van den Eijnden DH; McDowell W; Kelly VA; Witham SJ; Edbrooke MR; Bird MI; de Vries T; Smithers N 《Glycobiology》1998,8(4):321-327
The alpha3 fucosyltransferase, FucT-VII, is one of the key
glycosyltransferases involved in the biosynthesis of the sialyl Lewis X
(sLex) antigen on human leukocytes. The sialyl Lewis X antigen
(NeuAcalpha(2-3)Galbeta(1-4)[Fucalpha(1-3)]GlcNAc-R) is an essential
component of the recruitment of leukocytes to sites of inflammation,
mediating the primary interaction between circulating leukocytes and
activated endothelium. In order to characterize the enzymatic properties of
the leukocyte alpha3 fucosyltransferase FucT-VII, the enzyme has been
expressed in Trichoplusia ni insect cells. The enzyme is capable of
synthesizing both sLexand sialyl-dimeric-Lexstructures in vitro , from
3'-sialyl-lacNAc and VIM-2 structures, respectively, with only low levels
of fucose transfer observed to neutral or 3'-sulfated acceptors. Studies
using fucosylated NeuAcalpha(2-3)-(Galbeta(1- 4)GlcNAc)3-Me acceptors
demonstrate that FucT-VII is able to synthesize both di-fucosylated and
tri-fucosylated structures from mono- fucosylated precursors, but
preferentially fucosylates the distal GlcNAc within a polylactosamine
chain. Furthermore, the rate of fucosylation of the internal GlcNAc
residues is reduced once fucose has been added to the distal GlcNAc. These
results indicate that FucT-VII is capable of generating complex selectin
ligands, in vitro , however the order of fucose addition to the lactosamine
chain affects the rate of selectin ligand synthesis.
相似文献
169.
Hayley M Bennett Hoi Ping Mok Effrossyni Gkrania-Klotsas Isheng J Tsai Eleanor J Stanley Nagui M Antoun Avril Coghlan Bhavana Harsha Alessandra Traini Diogo M Ribeiro Sascha Steinbiss Sebastian B Lucas Kieren SJ Allinson Stephen J Price Thomas S Santarius Andrew J Carmichael Peter L Chiodini Nancy Holroyd Andrew F Dean Matthew Berriman 《Genome biology》2014,15(11)
170.
Goring DR Banks P Fallis L Baszczynski CL Beversdorf WD Rothstein SJ 《The Plant journal : for cell and molecular biology》1992,2(6):999-1003
We have previously described a developmentally regulated mRNA in maize that accumulates in mature embryos and is involved in a variety of stress responses in the plant. The sequence of the encoded 16 kDa protein (MA16) predicts that it is an RNA-binding protein, since it possesses a ribonucleoprotein consensus sequence-type RNA-binding domain (CS-RBD). To assess the predicted RNA binding property of the protein and as a starting point to characterize its function we have used ribohomopolymer-binding assays. Here we show that the MA16-encoded protein binds preferentially to uridine- and guanosine-rich RNAs. In light of these results a likely role for this protein in RNA metabolism during late embryogenesis and in the stress response is discussed. 相似文献