Article
|
Open Access
Featured
-
-
Article
| Open Access
Truncated FGFR2 is a clinically actionable oncogene in multiple cancers
Truncation of exon 18 of FGFR2 (FGFR2ΔE18) is a potent driver mutation in mice and humans, and FGFR-targeted therapy should be considered for patients with cancer expressing stable FGFR2ΔE18 variants.
- Daniel Zingg
- , Jinhyuk Bhin
- & Jos Jonkers
-
Article |
Glioblastoma mutations alter EGFR dimer structure to prevent ligand bias
Extracellular glioblastoma-associated mutations reduce the ability of the epidermal growth factor receptor to distinguish between its ligands.
- Chun Hu
- , Carlos A. Leche II
- & Mark A. Lemmon
-
Article
| Open Access
TMK-based cell-surface auxin signalling activates cell-wall acidification
Auxin induces transmembrane-kinase-dependent activation of H+-ATPase in the plasma membrane through phosphorylation of its penultimate threonine residue, promoting apoplastic acidification and hypocotyl cell elongation in Arabidopsis.
- Wenwei Lin
- , Xiang Zhou
- & Zhenbiao Yang
-
Article
| Open Access
The structure of neurofibromin isoform 2 reveals different functional states
Cryo-EM structure of Nf1 protein is reported, revealing closed and open conformations that regulate interaction with Ras oncogene, setting the stage for understanding the mechanistic action of Nf1 and how disease mutations lead to dysfunction.
- Andreas Naschberger
- , Rozbeh Baradaran
- & Marta Carroni
-
Article |
NOTUM from Apc-mutant cells biases clonal competition to initiate cancer
NOTUM from Apc-mutant cells acts as a key mediator during the early stages of mutation fixation and drives the formation of intestinal adenomas.
- Dustin J. Flanagan
- , Nalle Pentinmikko
- & Owen J. Sansom
-
Article |
MAP3K2-regulated intestinal stromal cells define a distinct stem cell niche
A subset of intestinal stromal cells that is regulated by the kinase MAP3K2 protects intestinal stem cells against injury by producing the WNT agonist R-spondin 1.
- Ningbo Wu
- , Hongxiang Sun
- & Bing Su
-
Article |
The gluconeogenic enzyme PCK1 phosphorylates INSIG1/2 for lipogenesis
Phosphorylation of INSIG1 and INSIG2 by PCK1 leads to a reduction in the binding of sterols, the activation of SREBP1 and SREBP2 and the downstream transcription of lipogenesis-associated genes that promote tumour growth.
- Daqian Xu
- , Zheng Wang
- & Zhimin Lu
-
Article |
Rapid non-uniform adaptation to conformation-specific KRAS(G12C) inhibition
Populations of KRAS(G12C)-mutant cancer cells can rapidly bypass the effects of treatment with KRAS(G12C) inhibitors because a subset of cells escapes drug-induced quiescence by producing new KRAS(G12C) that is maintained in its active, drug-insensitive state.
- Jenny Y. Xue
- , Yulei Zhao
- & Piro Lito
-
Article |
Architecture of autoinhibited and active BRAF–MEK1–14-3-3 complexes
The autoinhibited and active states of full-length BRAF in complexes with its substrate MEK1 and the 14-3-3 protein are determined by cryo-electron microscopy.
- Eunyoung Park
- , Shaun Rawson
- & Michael J. Eck
-
Letter |
Fatty acids and cancer-amplified ZDHHC19 promote STAT3 activation through S-palmitoylation
The palmitoylation of STAT3 is mediated by fatty acids and/or the palmitoyl acyltransferase ZDHHC19, and deregulation of this palmitoylation has a role in inflammation and tumorigenesis.
- Jixiao Niu
- , Yang Sun
- & Xu Wu
-
Letter |
UDP-glucose accelerates SNAI1 mRNA decay and impairs lung cancer metastasis
UDP-glucose has a tumour-suppressive role by inhibiting the association between HuR and SNAI1 mRNA, whereas UGDH-mediated metabolism of UDP-glucose leads to increased SNAI1 mRNA stability and expression, thereby promoting tumour cell migration and lung cancer metastasis.
- Xiongjun Wang
- , Ruilong Liu
- & Weiwei Yang
-
Review Article |
Nutrient acquisition strategies of mammalian cells
A review of cellular strategies for nutrient sensing and acquisition, including how these strategies can be exploited by cancer cells.
- Wilhelm Palm
- & Craig B. Thompson
-
Letter |
Genetic wiring maps of single-cell protein states reveal an off-switch for GPCR signalling
Random mutagenesis in haploid human cells coupled to quantitative protein measurements with different antibodies is used as a readout for individual cellular phenotypes.
- Markus Brockmann
- , Vincent A. Blomen
- & Thijn R. Brummelkamp
-
Letter |
Surrogate Wnt agonists that phenocopy canonical Wnt and β-catenin signalling
The authors describe water-soluble surrogate Wnt agonists, with specificity towards some frizzled (FZD) receptors, which can maintain human intestinal organoid cultures and have effects on the mouse liver in vivo.
- Claudia Y. Janda
- , Luke T. Dang
- & K. Christopher Garcia
-
Letter |
FGF-dependent metabolic control of vascular development
Fibroblast growth factor receptor (FGFR) signalling is a crucial regulator of endothelial metabolism and vascular development.
- Pengchun Yu
- , Kerstin Wilhelm
- & Michael Simons
-
Article |
Force interacts with macromolecular structure in activation of TGF-β
Integrin αVβ6 binds the transforming growth factor-β1 precursor (pro-TGF-β1) in an orientation that is biologically relevant for force-dependent release of TGF-β from its latent form.
- Xianchi Dong
- , Bo Zhao
- & Timothy A. Springer
-
Letter |
The ligand Sas and its receptor PTP10D drive tumour-suppressive cell competition
Wild-type Drosophila epithelial cells outcompete proto-oncogenic cells through translocation of the ligand Sas to the wild-type–tumour cell interface, where it binds the PTP10D receptor of the tumour cell, initiating pro-apoptotic signalling.
- Masatoshi Yamamoto
- , Shizue Ohsawa
- & Tatsushi Igaki
-
Letter |
Small molecule stabilization of the KSR inactive state antagonizes oncogenic Ras signalling
A class of small molecules that stabilize a previously unrecognized inactive state of KSR is reported; the agonists synergize with MEK inhibitors to prevent growth of Ras mutant cell lines.
- Neil S. Dhawan
- , Alex P. Scopton
- & Arvin C. Dar
-
Letter |
Visualization of a short-range Wnt gradient in the intestinal stem-cell niche
Generation of an epitope-tagged, functional Wnt3 knock-in allele, the signal produced by Paneth cells to regulate intestinal stem cells.
- Henner F. Farin
- , Ingrid Jordens
- & Hans Clevers
-
Letter |
Coordinated regulation of protein synthesis and degradation by mTORC1
mTORC1 is known to stimulate protein synthesis; now, it is shown to also promote the synthesis of proteasomes, which degrade proteins into the amino acids needed to create new proteins.
- Yinan Zhang
- , Justin Nicholatos
- & Brendan D. Manning
-
Letter |
Activation and repression by oncogenic MYC shape tumour-specific gene expression profiles
Inducing changes in the levels of the MYC oncoprotein is shown to activate and repress specific sets of target genes that are characteristic of tumour cells, providing an insight into the mechanism by which MYC can stimulate tumorigenesis in contrast to its physiological role.
- Susanne Walz
- , Francesca Lorenzin
- & Martin Eilers
-
Letter |
Cell-cycle-regulated activation of Akt kinase by phosphorylation at its carboxyl terminus
Phosphorylation of Akt at its carboxy-terminal tail is an essential layer of Akt activation to regulate its physiological functions.
- Pengda Liu
- , Michael Begley
- & Wenyi Wei
-
Article |
Temporal regulation of EGF signalling networks by the scaffold protein Shc1
The Shc1 scaffold mediates a switch in the signaling output of the epidermal growth factor receptor tyrosine kinase over time through recruitment of successive waves of proteins with distinct biological functions.
- Yong Zheng
- , Cunjie Zhang
- & Tony Pawson
-
Letter |
Small molecule inhibition of the KRAS–PDEδ interaction impairs oncogenic KRAS signalling
KRAS is one of the most frequently mutated oncogenes and a major target in anticancer drug discovery, but small molecule modulators that work in the clinic have been elusive; here a new approach to target KRAS is described, based on interfering with its binding to the prenyl-binding protein PDEδ.
- Gunther Zimmermann
- , Björn Papke
- & Herbert Waldmann
-
Article |
mTOR kinase structure, mechanism and regulation
Co-crystal structures of a number of complexes involving truncated mammalian target of rapamycin, a phosphoinositide 3-kinase-related protein kinase, reveal an intrinsically active kinase conformation and show how rapamycin–FKBP12 directly blocks substrate recruitment to the kinase domain.
- Haijuan Yang
- , Derek G. Rudge
- & Nikola P. Pavletich
-
Article |
Structure of the human smoothened receptor bound to an antitumour agent
The crystal structure of the human smoothened (SMO) receptor is presented in complex with a small-molecule antitumour agent; this represents the first example of a non-class-A, 7-transmembrane (7TM) receptor structure, revealing different conserved motifs common within class frizzled 7TM receptors and an unusually complex arrangement of long extracellular loops stabilized by disulphide bonds.
- Chong Wang
- , Huixian Wu
- & Raymond C. Stevens
-
Article |
PDGF signalling controls age-dependent proliferation in pancreatic β-cells
- Hainan Chen
- , Xueying Gu
- & Seung K. Kim
-
Research Highlights |
Cell biology: Communication key to cancer virus
-
News & Views |
Of worms and women
In roundworms, age-related decline in egg quality is regulated by specific humoral signalling pathways. If similar mechanisms operate in mammals, these findings may suggest ways to delay reproductive ageing in women.
- Kevin Flurkey
- & David E. Harrison
Control of neuronal excitation–inhibition balance by BMP–SMAD1 signalling