Abstract：
:Oncogenic activation of RAS genes via point mutations occurs in 20%-30% of human cancers. The development of effective RAS inhibitors has been challenging, necessitating new approaches to inhibit this oncogenic protein. Functional studies have shown that the switch region of RAS interacts with a large number of effector proteins containing a common RAS-binding domain (RBD). Because RBD-mediated interactions are essential for RAS signaling, blocking RBD association with small molecules constitutes an attractive therapeutic approach. Here, we present evidence that rigosertib, a styryl-benzyl sulfone, acts as a RAS-mimetic and interacts with the RBDs of RAF kinases, resulting in their inability to bind to RAS, disruption of RAF activation, and inhibition of the RAS-RAF-MEK pathway. We also find that ribosertib binds to the RBDs of Ral-GDS and PI3Ks. These results suggest that targeting of RBDs across multiple signaling pathways by rigosertib may represent an effective strategy for inactivation of RAS signaling.
journal_name
Celljournal_title
Cellauthors
Athuluri-Divakar SK,Vasquez-Del Carpio R,Dutta K,Baker SJ,Cosenza SC,Basu I,Gupta YK,Reddy MV,Ueno L,Hart JR,Vogt PK,Mulholland D,Guha C,Aggarwal AK,Reddy EPdoi
10.1016/j.cell.2016.03.045subject
Has Abstractpub_date
2016-04-21 00:00:00pages
643-55issue
3eissn
0092-8674issn
1097-4172pii
S0092-8674(16)30343-9journal_volume
165pub_type
杂志文章相关文献
CELL文献大全abstract：:During the process of chromatin diminution, which takes place in all presomatic cells of the early Ascaris embryo, the heterochromatic termini of the chromosomes are lost. Here we show that the newly formed ends of the reduced somatic chromosomes carry tandem repeats of the telomeric sequence TTAGGC. Comparison of a c...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(91)90076-b
更新日期：1991-11-15 00:00:00
abstract：:The immortal strand hypothesis posits that the propensity of stem cell compartments to give rise to cancer in later life can be minimized if stem cells, during the process of self-renewal, retain those DNA strands with the fewest mutations acquired during DNA replication. In this Essay, I explore evidence in support o...
journal_title：Cell
pub_type： 杂志文章,评审
doi：10.1016/j.cell.2007.06.019
更新日期：2007-06-29 00:00:00
abstract：:Steroid hormones induce transcription from the mouse mammary tumor virus (MMTV) promoter by complex mechanisms requiring binding of the hormone receptors to the hormone responsive element (HRE) of the long terminal repeat region. Here we show that the MMTV promoter contains two degenerated octamer motifs immediately u...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(91)90240-y
更新日期：1991-02-08 00:00:00
abstract：:The DNA-binding region of Myb consists of three imperfect tandem repeats (R1, R2, and R3). We have determined the solution structure of a specific DNA complex of the minimum DNA-binding domain (R2R3) by heteronuclear multidimensional NMR. Both R2 and R3 contain three helices, and the third helix in each is found to be...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(94)90549-5
更新日期：1994-11-18 00:00:00
abstract：:In ciliates, small RNAs have been shown to target foreign sequences for silencing via elimination from the somatic genome. Fang et al. now reveal a set of Piwi-interacting RNAs (piRNAs) in Oxytricha trifallax that likewise enable genomic self versus nonself discrimination, this time by specifying self sequences for ge...
journal_title：Cell
pub_type： 评论,杂志文章
doi：10.1016/j.cell.2012.11.032
更新日期：2012-12-07 00:00:00
abstract：:The 90S pre-ribosome is an early biogenesis intermediate formed during co-transcriptional ribosome formation, composed of ∼70 assembly factors and several small nucleolar RNAs (snoRNAs) that associate with nascent pre-rRNA. We report the cryo-EM structure of the Chaetomium thermophilum 90S pre-ribosome, revealing how ...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2016.06.014
更新日期：2016-07-14 00:00:00
abstract：:In dividing cells, nuclear pore complexes (NPCs) disassemble during mitosis and reassemble into the newly forming nuclei. However, the fate of nuclear pores in postmitotic cells is unknown. Here, we show that NPCs, unlike other nuclear structures, do not turn over in differentiated cells. While a subset of NPC compone...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2008.11.037
更新日期：2009-01-23 00:00:00
abstract：:Pulmonary neuroendocrine (NE) cells are neurosensory cells sparsely distributed throughout the bronchial epithelium, many in innervated clusters of 20-30 cells. Following lung injury, NE cells proliferate and generate other cell types to promote epithelial repair. Here, we show that only rare NE cells, typically 2-4 p...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2019.09.010
更新日期：2019-10-03 00:00:00
abstract：:AMPA receptors mediate fast excitatory neurotransmission in the mammalian brain and transduce the binding of presynaptically released glutamate to the opening of a transmembrane cation channel. Within the postsynaptic density, however, AMPA receptors coassemble with transmembrane AMPA receptor regulatory proteins (TAR...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2017.07.045
更新日期：2017-09-07 00:00:00
abstract：:H2S is an endogenous gasotransmitter that plays an important role in physiological conditions. In this issue, Das et al. provide evidence that SIRT1-dependent angiogenesis is augmented by H2S-findings reinforced by Longchamp et al., who demonstrate that H2S-dependent angiogenesis is triggered by amino acid deprivation...
journal_title：Cell
pub_type： 评论,杂志文章
doi：10.1016/j.cell.2018.03.011
更新日期：2018-03-22 00:00:00
abstract：:The Reelin ligand regulates a Dab1-dependent signaling pathway required for brain lamination and normal dendritogenesis, but the specific mechanisms underlying these actions remain unclear. We find that Stk25, a modifier of Reelin-Dab1 signaling, regulates Golgi morphology and neuronal polarization as part of an LKB1-...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2010.10.029
更新日期：2010-11-24 00:00:00
abstract：:While the tumor suppressor functions of p53 have long been recognized, the contribution of p53 to numerous other aspects of disease and normal life is only now being appreciated. This burgeoning range of responses to p53 is reflected by an increasing variety of mechanisms through which p53 can function, although the a...
journal_title：Cell
pub_type： 杂志文章,评审
doi：10.1016/j.cell.2009.04.037
更新日期：2009-05-01 00:00:00
abstract：:S. cerevisiae inherits its vacuole by projecting vacuole-derived membrane vesicles and tubules into the bud, where they fuse to establish the daughter vacuole. This homotypic fusion event can be assayed in vitro. It requires Sec17p and Sec18p, the homologs of the mammalian alpha-SNAP and NSF, which cooperate in multip...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/s0092-8674(00)81084-3
更新日期：1996-04-05 00:00:00
abstract：:The messenger RNA coding for the precursor of the small subunit of ribulose--1,5--bisphosphate (Ru-P2) carboxylase has been partially purified from pea leaves. The mRNA has a size of 11.5S, is approximately 800 nucleotides long and, on cell-free translation, directs the synthesis of a single major polypeptide of 20,00...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(79)90164-8
更新日期：1979-06-01 00:00:00
abstract：:RECQL5 is the sole member of the RECQ family of helicases associated with RNA polymerase II (RNAPII). We now show that RECQL5 is a general elongation factor that is important for preserving genome stability during transcription. Depletion or overexpression of RECQL5 results in corresponding shifts in the genome-wide R...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2014.03.048
更新日期：2014-05-22 00:00:00
abstract：:The v-erbB gene product of avian erythroblastosis virus (AEV) has extensive homology with the receptor for epidermal growth factor (EGF). We report here that chicken embryo fibroblasts (CEF) transformed by AEV show enhanced tyrosine phosphorylation of a number of cellular polypeptides, including the 36 kd protein, whi...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(85)90209-0
更新日期：1985-03-01 00:00:00
abstract：:The 2.2 kb mRNA of the Dictyostelium discoideum prespore gene EB4-PSV is constitutively transcribed during growth and development, but the message is only accumulated when cells form aggregates and establish the prespore-prestalk pattern. Disruption of the pattern by mechanical disaggregation results in a rapid loss o...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(92)90130-5
更新日期：1992-04-03 00:00:00
abstract：:A gene for Saccharomyces cerevisiae tRNATrp has been sequenced which contains an intervening sequence of 34 bp (H. S. Kang and J. Abelson, unpublished results). The mutant yeast strain ts-136 accumulates a precursor to tRNATrp which contains mature ends and is colinear with the tRNATrp gene. A nuclear extract from Xen...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(79)90166-1
更新日期：1979-06-01 00:00:00
abstract：:Phosphodiesterases (PDEs) regulate the local concentration of 3',5' cyclic adenosine monophosphate (cAMP) within cells. cAMP activates the cAMP-dependent protein kinase (PKA). In patients, PDE inhibitors have been linked to heart failure and cardiac arrhythmias, although the mechanisms are not understood. We show that...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2005.07.030
更新日期：2005-10-07 00:00:00
abstract：:Ocean microbial communities strongly influence the biogeochemistry, food webs, and climate of our planet. Despite recent advances in understanding their taxonomic and genomic compositions, little is known about how their transcriptomes vary globally. Here, we present a dataset of 187 metatranscriptomes and 370 metagen...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2019.10.014
更新日期：2019-11-14 00:00:00
abstract：:The specificity of target gene activation by steroid receptors is encoded within a small, cysteine-rich domain that is believed to form two zinc-coordinated fingers. Here we show that the ability of glucocorticoid and estrogen receptors to discriminate between their closely related response elements resides in the two...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(89)90050-0
更新日期：1989-06-30 00:00:00
abstract：:Bacteria have evolved many different means of generating movement. In this issue of Cell, Shaevitz et al. (2005) describe the swimming movement of a helical bacterium called Spiroplasma. They discover that Spiroplasma propels itself by generating two temporally distinct kinks that travel the length of the bacterium. T...
journal_title：Cell
pub_type： 评论,杂志文章,评审
doi：10.1016/j.cell.2005.09.003
更新日期：2005-09-23 00:00:00
abstract：:To study the insertion of multispanning membrane proteins into the endoplasmic reticulum, we constructed novel proteins on the cDNA level by repeating, up to four times, the internal signal-anchor domain of the asialoglycoprotein receptor H1. Upon in vitro translation in the presence of microsomes, these polypeptides ...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(88)90009-8
更新日期：1988-10-07 00:00:00
abstract：:A cDNA library has been constructed from an RNA preparation highly enriched in silkmoth chorion mRNAs. Many distinct clones have been identified from this library using a stepwise procedure: scoring for infrequent hexanucleotide restriction enzyme recognition sequences; detailed characterization with restriction enzym...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(79)90241-1
更新日期：1979-12-01 00:00:00
abstract：:Meyer et al. find that subjects lacking the AIRE gene, critical for self-tolerance in T lymphocytes, show a broad range of autoantibody specificities, which can have extremely high affinities. The data also suggest that some of these autoantibodies can, surprisingly, prevent some types of autoimmunity, particularly ty...
journal_title：Cell
pub_type： 评论,杂志文章
doi：10.1016/j.cell.2016.07.018
更新日期：2016-07-28 00:00:00
abstract：:O(2) is the ultimate electron acceptor for mitochondrial respiration, a process catalyzed by cytochrome c oxidase (COX). In yeast, COX subunit composition is regulated by COX5a and COX5b gene transcription in response to high and low O(2), respectively. Here we demonstrate that in mammalian cells, expression of the CO...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/j.cell.2007.01.047
更新日期：2007-04-06 00:00:00
abstract：:The elucidation of the genetic code remains among the most influential discoveries in biology. While innumerable studies have validated the general universality of the code and its value in predicting and analyzing protein coding sequences, established and emerging work has also suggested that full genome decryption m...
journal_title：Cell
pub_type： 杂志文章,评审
doi：10.1016/j.cell.2016.09.022
更新日期：2016-12-15 00:00:00
abstract：:A key step in the regulation of transcription involves interactions between promoter-selective factors and various components of the transcriptional apparatus. Here we report the requirements for transcriptional activation directed by NTF-1, a developmentally regulated transcription factor in Drosophila. Reconstituted...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(81)90019-2
更新日期：1991-08-09 00:00:00
abstract：:Previous work from our laboratory has demonstrated that a subclass of the aminoglycoside antibiotics, those containing the drug fragment paromamine, stimulates mistranslation in cell-free protein-synthesizing systems derived from eucaryotic cells. We report here experiments which show that the ciliate Tetrahymena ther...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(78)90201-5
更新日期：1978-02-01 00:00:00
abstract：:NRK fibroblasts exposed to transforming growth factor-beta (TGF-beta) show increased binding of radiolabeled epidermal growth factor (EGF) relative to untreated cells. The binding of another growth factor, rat insulin-like growth factor-II, is unaffected. The increase in EGF binding induced by TGF-beta is not due to i...
journal_title：Cell
pub_type： 杂志文章
doi：10.1016/0092-8674(84)90071-0
更新日期：1984-01-01 00:00:00
