Adaptive endoplasmic reticulum stress signalling via IRE1α-XBP1 preserves self-renewal of haematopoietic and pre-leukaemic stem cells.

Abstract:

:Over their lifetime, long-term haematopoietic stem cells (HSC) are exposed to a variety of stress conditions that they must endure. Many stresses, such as infection/inflammation, reactive oxygen species, nutritional deprivation and hypoxia, activate unfolded protein response signalling, which induces either adaptive changes to resolve the stress or apoptosis to clear the damaged cell. Whether unfolded-protein-response signalling plays any role in HSC regulation remains to be established. Here, we report that the adaptive signalling of the unfolded protein response, IRE1α-XBP1, protects HSCs from endoplasmic reticulum stress-induced apoptosis. IRE1α knockout leads to reduced reconstitution of HSCs. Furthermore, we show that oncogenic N-RasG12D activates IRE1α-XBP1, through MEK-GSK3β, to promote HSC survival under endoplasmic reticulum stress. Inhibiting IRE1α-XBP1 abolished N-RasG12D-mediated survival under endoplasmic reticulum stress and diminished the competitive advantage of NrasG12D HSCs in transplant recipients. Our studies illuminate how the adaptive endoplasmic reticulum stress response is advantageous in sustaining self-renewal of HSCs and promoting pre-leukaemic clonal dominance.

journal_name

Nat Cell Biol

journal_title

Nature cell biology

authors

Liu L,Zhao M,Jin X,Ney G,Yang KB,Peng F,Cao J,Iwawaki T,Del Valle J,Chen X,Li Q

doi

10.1038/s41556-019-0285-6

subject

Has Abstract

pub_date

2019-03-01 00:00:00

pages

328-337

issue

3

eissn

1465-7392

issn

1476-4679

pii

10.1038/s41556-019-0285-6

journal_volume

21

pub_type

杂志文章
  • Vesicles modulate an actin network for asymmetric spindle positioning.

    abstract::Actin networks drive many essential cellular processes, including cell migration, cytokinesis and tissue morphogenesis. However, how cells organize and regulate dynamic actin networks that consist of long, unbranched actin filaments is only poorly understood. This study in mouse oocytes reveals that cells can use vesi...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb2802

    authors: Holubcová Z,Howard G,Schuh M

    更新日期:2013-08-01 00:00:00

  • Oxidant-induced apoptosis is mediated by oxidation of the actin-regulatory protein cofilin.

    abstract::Physiological oxidants that are generated by activated phagocytes comprise the main source of oxidative stress during inflammation. Oxidants such as taurine chloramine (TnCl) and hydrogen peroxide (H(2)O(2)) can damage proteins and induce apoptosis, but the role of specific protein oxidation in this process has not be...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb1968

    authors: Klamt F,Zdanov S,Levine RL,Pariser A,Zhang Y,Zhang B,Yu LR,Veenstra TD,Shacter E

    更新日期:2009-10-01 00:00:00

  • The armadillo protein p0071 regulates Rho signalling during cytokinesis.

    abstract::Cytokinesis requires the spatio-temporal coordination of cell-cycle control and cytoskeletal reorganization. Members of the Rho-family of GTPases are crucial regulators of this process and assembly of the contractile ring depends on local activation of Rho signalling. Here, we show that the armadillo protein p0071, un...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb1504

    authors: Wolf A,Keil R,Götzl O,Mun A,Schwarze K,Lederer M,Hüttelmaier S,Hatzfeld M

    更新日期:2006-12-01 00:00:00

  • Classifying collective cancer cell invasion.

    abstract::Most invasive solid tumours display predominantly collective invasion, in which groups of cells invade the peritumoral stroma while maintaining cell-cell contacts. As the concepts and experimental models for functional analysis of collective cancer cell invasion are rapidly developing, we propose a framework for addre...

    journal_title:Nature cell biology

    pub_type: 杂志文章,评审

    doi:10.1038/ncb2548

    authors: Friedl P,Locker J,Sahai E,Segall JE

    更新日期:2012-08-01 00:00:00

  • Systems analysis of RhoGEF and RhoGAP regulatory proteins reveals spatially organized RAC1 signalling from integrin adhesions.

    abstract::Rho GTPases are central regulators of the cytoskeleton and, in humans, are controlled by 145 multidomain guanine nucleotide exchange factors (RhoGEFs) and GTPase-activating proteins (RhoGAPs). How Rho signalling patterns are established in dynamic cell spaces to control cellular morphogenesis is unclear. Through a fam...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/s41556-020-0488-x

    authors: Müller PM,Rademacher J,Bagshaw RD,Wortmann C,Barth C,van Unen J,Alp KM,Giudice G,Eccles RL,Heinrich LE,Pascual-Vargas P,Sanchez-Castro M,Brandenburg L,Mbamalu G,Tucholska M,Spatt L,Czajkowski MT,Welke RW,Zhang S,Ngu

    更新日期:2020-04-01 00:00:00

  • Arabidopsis HT1 kinase controls stomatal movements in response to CO2.

    abstract::Guard cells, which form stomata in leaf epidermes, sense a multitude of environmental signals and integrate this information to regulate stomatal movements. Compared with the advanced understanding of light and water stress responses in guard cells, the molecular mechanisms that underlie stomatal CO(2) signalling have...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb1387

    authors: Hashimoto M,Negi J,Young J,Israelsson M,Schroeder JI,Iba K

    更新日期:2006-04-01 00:00:00

  • Single-cell technologies sharpen up mammalian stem cell research.

    abstract::Analysis of the mechanisms underlying cell fates requires the molecular quantification of cellular features. Classical techniques use population average readouts at single time points. However, these approaches mask cellular heterogeneity and dynamics and are limited for studying rare and heterogeneous cell population...

    journal_title:Nature cell biology

    pub_type: 杂志文章,评审

    doi:10.1038/ncb3042

    authors: Hoppe PS,Coutu DL,Schroeder T

    更新日期:2014-10-01 00:00:00

  • Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation.

    abstract::The heterogeneity of exosomal populations has hindered our understanding of their biogenesis, molecular composition, biodistribution and functions. By employing asymmetric flow field-flow fractionation (AF4), we identified two exosome subpopulations (large exosome vesicles, Exo-L, 90-120 nm; small exosome vesicles, Ex...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/s41556-018-0040-4

    authors: Zhang H,Freitas D,Kim HS,Fabijanic K,Li Z,Chen H,Mark MT,Molina H,Martin AB,Bojmar L,Fang J,Rampersaud S,Hoshino A,Matei I,Kenific CM,Nakajima M,Mutvei AP,Sansone P,Buehring W,Wang H,Jimenez JP,Cohen-Gould L,P

    更新日期:2018-03-01 00:00:00

  • CK1α suppresses lung tumour growth by stabilizing PTEN and inducing autophagy.

    abstract::The contribution of autophagy to cancer development remains controversial, largely owing to the fact that autophagy can be tumour suppressive or oncogenic in different biological contexts. Here, we show that in non-small-cell lung cancer (NSCLC), casein kinase 1 alpha 1 (CK1α) suppresses tumour growth by functioning a...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/s41556-018-0065-8

    authors: Cai J,Li R,Xu X,Zhang L,Lian R,Fang L,Huang Y,Feng X,Liu X,Li X,Zhu X,Zhang H,Wu J,Zeng M,Song E,He Y,Yin Y,Li J,Li M

    更新日期:2018-04-01 00:00:00

  • SHARPIN is an endogenous inhibitor of β1-integrin activation.

    abstract::Regulated activation of integrins is critical for cell adhesion, motility and tissue homeostasis. Talin and kindlins activate β1-integrins, but the counteracting inhibiting mechanisms are poorly defined. We identified SHARPIN as an important inactivator of β1-integrins in an RNAi screen. SHARPIN inhibited β1-integrin ...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb2340

    authors: Rantala JK,Pouwels J,Pellinen T,Veltel S,Laasola P,Mattila E,Potter CS,Duffy T,Sundberg JP,Kallioniemi O,Askari JA,Humphries MJ,Parsons M,Salmi M,Ivaska J

    更新日期:2011-09-25 00:00:00

  • Protein complexes containing CYFIP/Sra/PIR121 coordinate Arf1 and Rac1 signalling during clathrin-AP-1-coated carrier biogenesis at the TGN.

    abstract::Actin dynamics is a tightly regulated process involved in various cellular events including biogenesis of clathrin-coated, AP-1 (adaptor protein 1)-coated transport carriers connecting the trans-Golgi network (TGN) and the endocytic pathway. However, the mechanisms coordinating coat assembly, membrane and actin remode...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb2034

    authors: Anitei M,Stange C,Parshina I,Baust T,Schenck A,Raposo G,Kirchhausen T,Hoflack B

    更新日期:2010-04-01 00:00:00

  • PI-loting membrane traffic.

    abstract::Phosphoinositides (PIs) undergo phosphorylation/dephosphorylation cycles through organelle-specific PI kinases and PI phosphatases that lead to distinct subcellular distributions of the individual PI species. Specific PIs control the correct timing and location of many trafficking events. Their ultimate mode of action...

    journal_title:Nature cell biology

    pub_type: 杂志文章,评审

    doi:10.1038/ncb0604-487

    authors: De Matteis MA,Godi A

    更新日期:2004-06-01 00:00:00

  • Mapping phospho-catalytic dependencies of therapy-resistant tumours reveals actionable vulnerabilities.

    abstract::Phosphorylation networks intimately regulate mechanisms of response to therapies. Mapping the phospho-catalytic profile of kinases in cells or tissues remains a challenge. Here, we introduce a practical high-throughput system to measure the enzymatic activity of kinases using biological peptide targets as phospho-sens...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/s41556-019-0328-z

    authors: Coppé JP,Mori M,Pan B,Yau C,Wolf DM,Ruiz-Saenz A,Brunen D,Prahallad A,Cornelissen-Steijger P,Kemper K,Posch C,Wang C,Dreyer CA,Krijgsman O,Lee PRE,Chen Z,Peeper DS,Moasser MM,Bernards R,van 't Veer LJ

    更新日期:2019-06-01 00:00:00

  • Molecular basis for the functional interaction of dynein light chain with the nuclear-pore complex.

    abstract::Nucleocytoplasmic transport occurs through nuclear pore complexes (NPCs) embedded in the nuclear envelope. Here, we discovered an unexpected role for yeast dynein light chain (Dyn2) in the NPC. Dyn2 is a previously undescribed nucleoporin that functions as molecular glue to dimerize and stabilize the Nup82-Nsp1-Nup159...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb1604

    authors: Stelter P,Kunze R,Flemming D,Höpfner D,Diepholz M,Philippsen P,Böttcher B,Hurt E

    更新日期:2007-07-01 00:00:00

  • p53-Driven apoptosis limits centrosome amplification and genomic instability downstream of NPM1 phosphorylation.

    abstract::Chromosome loss or gain is associated with a large number of solid cancers, providing genomic plasticity and thus adaptability to cancer cells. Numerical centrosome abnormalities arising from centrosome over-duplication or failed cytokinesis are a recognized cause of aneuploidy. In higher eukaryotic cells, the centros...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb1735

    authors: Cuomo ME,Knebel A,Morrice N,Paterson H,Cohen P,Mittnacht S

    更新日期:2008-06-01 00:00:00

  • Loss of nucleoplasmic LAP2alpha-lamin A complexes causes erythroid and epidermal progenitor hyperproliferation.

    abstract::Lamina-associated polypeptide (LAP) 2alpha is a chromatin-associated protein that binds A-type lamins. Mutations in both LAP2alpha and A-type lamins are linked to human diseases called laminopathies, but the molecular mechanisms are poorly understood. The A-type lamin-LAP2alpha complex interacts with and regulates ret...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb1793

    authors: Naetar N,Korbei B,Kozlov S,Kerenyi MA,Dorner D,Kral R,Gotic I,Fuchs P,Cohen TV,Bittner R,Stewart CL,Foisner R

    更新日期:2008-11-01 00:00:00

  • COPII and the regulation of protein sorting in mammals.

    abstract::Secretory proteins are transported to the Golgi complex in vesicles that bud from the endoplasmic reticulum. The cytoplasmic coat protein complex II (COPII) is responsible for cargo sorting and vesicle morphogenesis. COPII was first described in Saccharomyces cerevisiae, but its basic function is conserved throughout ...

    journal_title:Nature cell biology

    pub_type: 杂志文章,评审

    doi:10.1038/ncb2390

    authors: Zanetti G,Pahuja KB,Studer S,Shim S,Schekman R

    更新日期:2011-12-22 00:00:00

  • New neuropeptides containing carboxy-terminal RFamide and their receptor in mammals.

    abstract::Only a few RFamide peptides have been identified in mammals, although they have been abundantly found in invertebrates. Here we report the identification of a human gene that encodes at least three RFamide-related peptides, hRFRP-1-3. Cells transfected with a seven-transmembrane-domain receptor, OT7T022, specifically ...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/35036326

    authors: Hinuma S,Shintani Y,Fukusumi S,Iijima N,Matsumoto Y,Hosoya M,Fujii R,Watanabe T,Kikuchi K,Terao Y,Yano T,Yamamoto T,Kawamata Y,Habata Y,Asada M,Kitada C,Kurokawa T,Onda H,Nishimura O,Tanaka M,Ibata Y,Fujino M

    更新日期:2000-10-01 00:00:00

  • Protein kinase activity of phosphoinositide 3-kinase regulates beta-adrenergic receptor endocytosis.

    abstract::Phosphoinositide 3-kinase (PI(3)K) is a unique enzyme characterized by both lipid and protein kinase activities. Here, we demonstrate a requirement for the protein kinase activity of PI(3)K in agonist-dependent beta-adrenergic receptor (betaAR) internalization. Using PI(3)K mutants with either protein or lipid phospho...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb1278

    authors: Naga Prasad SV,Jayatilleke A,Madamanchi A,Rockman HA

    更新日期:2005-08-01 00:00:00

  • The primary cilium and lipophagy translate mechanical forces to direct metabolic adaptation of kidney epithelial cells.

    abstract::Organs and cells must adapt to shear stress induced by biological fluids, but how fluid flow contributes to the execution of specific cell programs is poorly understood. Here we show that shear stress favours mitochondrial biogenesis and metabolic reprogramming to ensure energy production and cellular adaptation in ki...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/s41556-020-0566-0

    authors: Miceli C,Roccio F,Penalva-Mousset L,Burtin M,Leroy C,Nemazanyy I,Kuperwasser N,Pontoglio M,Friedlander G,Morel E,Terzi F,Codogno P,Dupont N

    更新日期:2020-09-01 00:00:00

  • Noelin-1 is a secreted glycoprotein involved in generation of the neural crest.

    abstract::The vertebrate neural crest arises at the border of the neural plate during early stages of nervous system development; however, little is known about the molecular mechanisms underlying neural crest formation. Here we identify a secreted protein, Noelin-1, which has the ability to prolong neural crest production. Noe...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/35008643

    authors: Barembaum M,Moreno TA,LaBonne C,Sechrist J,Bronner-Fraser M

    更新日期:2000-04-01 00:00:00

  • Publisher Correction: Early lineage segregation of multipotent embryonic mammary gland progenitors.

    abstract::In the version of this Article originally published, ref. 52 was incorrectly only attributed to its corresponding author, Fre, S., and an older title was used. The correct citation should have been: Lilja, A. M. et al. Clonal analysis of Notch1-expressing cells reveals the existence of unipotent stem cells that retain...

    journal_title:Nature cell biology

    pub_type: 已发布勘误

    doi:10.1038/s41556-018-0164-6

    authors: Wuidart A,Sifrim A,Fioramonti M,Matsumura S,Brisebarre A,Brown D,Centonze A,Dannau A,Dubois C,Van Keymeulen A,Voet T,Blanpain C

    更新日期:2018-09-01 00:00:00

  • Protein dislocation from the ER requires polyubiquitination and the AAA-ATPase Cdc48.

    abstract::Endoplasmic reticulum (ER)-associated protein degradation by the ubiquitin-proteasome system requires the dislocation of substrates from the ER into the cytosol. It has been speculated that a functional ubiquitin proteasome pathway is not only essential for proteolysis, but also for the preceding export step. Here, we...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb746

    authors: Jarosch E,Taxis C,Volkwein C,Bordallo J,Finley D,Wolf DH,Sommer T

    更新日期:2002-02-01 00:00:00

  • PP2A activates brassinosteroid-responsive gene expression and plant growth by dephosphorylating BZR1.

    abstract::When brassinosteroid levels are low, the GSK3-like kinase BIN2 phosphorylates and inactivates the BZR1 transcription factor to inhibit growth in plants. Brassinosteroid promotes growth by inducing dephosphorylation of BZR1, but the phosphatase that dephosphorylates BZR1 has remained unknown. Here, using tandem affinit...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb2151

    authors: Tang W,Yuan M,Wang R,Yang Y,Wang C,Oses-Prieto JA,Kim TW,Zhou HW,Deng Z,Gampala SS,Gendron JM,Jonassen EM,Lillo C,DeLong A,Burlingame AL,Sun Y,Wang ZY

    更新日期:2011-02-01 00:00:00

  • MicroRNA-199b targets the nuclear kinase Dyrk1a in an auto-amplification loop promoting calcineurin/NFAT signalling.

    abstract::MicroRNAs (miRs) are a class of single-stranded, non-coding RNAs of about 22 nucleotides in length. Increasing evidence implicates miRs in myocardial disease processes. Here we show that miR-199b is a direct calcineurin/NFAT target gene that increases in expression in mouse and human heart failure, and targets the nuc...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb2126

    authors: da Costa Martins PA,Salic K,Gladka MM,Armand AS,Leptidis S,el Azzouzi H,Hansen A,Coenen-de Roo CJ,Bierhuizen MF,van der Nagel R,van Kuik J,de Weger R,de Bruin A,Condorelli G,Arbones ML,Eschenhagen T,De Windt LJ

    更新日期:2010-12-01 00:00:00

  • PDK1 regulates cancer cell motility by antagonising inhibition of ROCK1 by RhoE.

    abstract::In three-dimensional matrices cancer cells move with a rounded, amoeboid morphology that is controlled by ROCK-dependent contraction of acto-myosin. In this study, we show that PDK1 is required for phosphorylation of myosin light chain and cell motility, both on deformable gels and in vivo. Depletion of PDK1 alters th...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb1675

    authors: Pinner S,Sahai E

    更新日期:2008-02-01 00:00:00

  • The APC is dispensable for first meiotic anaphase in Xenopus oocytes.

    abstract::Here we show that segregation of homologous chromosomes and that of sister chromatids are differentially regulated in Xenopus and possibly in other higher eukaryotes. Upon hormonal stimulation, Xenopus oocytes microinjected with antibodies against the anaphase-promoting complex (APC) activator Fizzy or the APC core su...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/35050607

    authors: Peter M,Castro A,Lorca T,Le Peuch C,Magnaghi-Jaulin L,Dorée M,Labbé JC

    更新日期:2001-01-01 00:00:00

  • GENERATIVE CELL SPECIFIC 1 is essential for angiosperm fertilization.

    abstract::The double fertilization process in angiosperms is based on the delivery of a pair of sperm cells by the pollen tube (the male gametophyte), which elongates towards an embryo sac (the female gametophyte) enclosing an egg and a central cell. Several studies have described the mechanisms of gametophyte interaction, and ...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb1345

    authors: Mori T,Kuroiwa H,Higashiyama T,Kuroiwa T

    更新日期:2006-01-01 00:00:00

  • The Nup107-160 complex and gamma-TuRC regulate microtubule polymerization at kinetochores.

    abstract::The metazoan nuclear pore complex (NPC) disassembles during mitosis, and many of its constituents distribute onto spindles and kinetochores, including the Nup107-160 sub-complex. We have found that Nup107-160 interacts with the gamma-tubulin ring complex (gamma-TuRC), an essential and conserved microtubule nucleator, ...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb2016

    authors: Mishra RK,Chakraborty P,Arnaoutov A,Fontoura BM,Dasso M

    更新日期:2010-02-01 00:00:00

  • Regulation of RNA-polymerase-II-dependent transcription by N-WASP and its nuclear-binding partners.

    abstract::The presence of actin in the nucleus has been well established, and several studies have implicated nuclear actin in transcriptional regulation. Neuronal Wiskott-Aldrich syndrome protein (N-WASP) is a member of the WASP family of proteins; these proteins function in the cytoplasm as key regulators of cortical actin fi...

    journal_title:Nature cell biology

    pub_type: 杂志文章

    doi:10.1038/ncb1433

    authors: Wu X,Yoo Y,Okuhama NN,Tucker PW,Liu G,Guan JL

    更新日期:2006-07-01 00:00:00