Research Topics
Genomes and Genes | Harald StenmarkSummaryAffiliation: University of Oslo Country: Norway Publications
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Publications
A dual function for Deep orange in programmed autophagy in the Drosophila melanogaster fat bodyKarine Lindmo
Department of Biochemistry, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway
Exp Cell Res 312:2018-27. 2006..These results indicate that Dor controls autophagy indirectly, via ecdysone signaling, as well as directly, via autolysosomal fusion...
The phosphatidylinositol 3-phosphate-binding FYVE fingerHarald Stenmark
Department of Biochemistry, The Norwegian Radium Hospital, Oslo, Norway
FEBS Lett 513:77-84. 2002..Here we review recent work that sheds light on the targeting of FYVE finger proteins to PI3P-containing membranes, and how these proteins serve to regulate multiple cellular functions...
Autophagic degradation of dBruce controls DNA fragmentation in nurse cells during late Drosophila melanogaster oogenesisIoannis P Nezis
Centre for Cancer Biomedicine, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
J Cell Biol 190:523-31. 2010..Our results reveal autophagic degradation of an IAP as a novel mechanism of triggering cell death and thereby provide a mechanistic link between autophagy and cell death...
Ref(2)P, the Drosophila melanogaster homologue of mammalian p62, is required for the formation of protein aggregates in adult brainIoannis P Nezis
Department of Biochemistry, Centre for Cancer Biomedicine, University of Oslo and Institute for Cancer Research, The Norwegian Radium Hospital, N 0310 Oslo, Norway
J Cell Biol 180:1065-71. 2008..Our findings reveal a major role for Ref(2)P in the formation of ubiquitin-positive protein aggregates both under physiological conditions and when normal protein turnover is inhibited...
Eap45 in mammalian ESCRT-II binds ubiquitin via a phosphoinositide-interacting GLUE domainThomas Slagsvold
Department of Biochemistry, The Norwegian Radium Hospital, Montebello, Oslo
J Biol Chem 280:19600-6. 2005..Furthermore, we show that Eap45 colocalizes with ubiquitinated proteins on late endosomes. These results are consistent with a role for Eap45 in endosomal sorting of ubiquitinated cargo...
The selective macroautophagic degradation of aggregated proteins requires the PI3P-binding protein AlfyMaria Filimonenko
Centre for Cancer Biomedicine, University of Oslo, Department of Biochemistry, The Norwegian Radium Hospital, Oslo, Norway
Mol Cell 38:265-79. 2010..We propose that Alfy plays a key role in selective macroautophagy by bridging cargo to the molecular machinery that builds autophagosomes...
Differential functions of Hrs and ESCRT proteins in endocytic membrane traffickingCamilla Raiborg
Centre for Cancer Biomedicine, University of Oslo, and Department of Biochemistry, The Norwegian Radium Hospital, Rikshospitalet, Norway
Exp Cell Res 314:801-13. 2008....
Flat clathrin coats on endosomes mediate degradative protein sorting by scaffolding Hrs in dynamic microdomainsCamilla Raiborg
Department of Biochemistry, Institute for Cancer Research, the Norwegian Radium Hospital and the University of Oslo, Montebello, N 0310 Oslo, Norway
J Cell Sci 119:2414-24. 2006..We conclude that clathrin is responsible for concentrating Hrs in endosomal microdomains specialised for recognition of ubiquitylated membrane proteins, thus enabling efficient sorting of cargo into the degradative pathway...
Multivesicular endosome biogenesis in the absence of ESCRTsSusanne Stuffers
Department of Biochemistry, Institute for Cancer Research, The Norwegian Radiumhospital and Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Montebello, N 0310 Oslo, Norway
Traffic 10:925-37. 2009..Our observations suggest that both ESCRT-dependent and ESCRT-independent mechanisms of MVE biogenesis exist in mammalian cells...
The ESCRT-III subunit hVps24 is required for degradation but not silencing of the epidermal growth factor receptorKristi G Bache
Department of Biochemistry, Institute for Cancer Research, Norwegian Radium Hospital, Montebello, N 0310 Oslo, Norway
Mol Biol Cell 17:2513-23. 2006..Together, our results reveal functional differences between ESCRT-I and ESCRT-III in degradative protein trafficking and indicate that degradation of the EGFR is not required for termination of its signaling...
Disruption of Vps4 and JNK function in Drosophila causes tumour growthLina M Rodahl
Faculty of Medicine, Centre for Cancer Biomedicine, University of Oslo and Institute for Cancer Research, The Norwegian Radium Hospital, Rikshospitalet University Hospital, Montebello, Oslo, Norway
PLoS ONE 4:e4354. 2009..We conclude that dvps4 is a tumour suppressor in Drosophila and that JNK is central to the cell-autonomous phenotypes of ESCRT-deficient cells...
Alix regulates cortical actin and the spatial distribution of endosomesAlicia Cabezas
Department of Biochemistry, The Norwegian Radium Hospital, Montebello, Oslo
J Cell Sci 118:2625-35. 2005....
Cargo-dependent degradation of ESCRT-I as a feedback mechanism to modulate endosomal sortingLene Malerød
Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Montebello, Oslo, Norway
Traffic 12:1211-26. 2011....
Fab1 phosphatidylinositol 3-phosphate 5-kinase controls trafficking but not silencing of endocytosed receptorsTor Erik Rusten
Department of Biochemistry, the Norwegian Radium Hospital and the University of Oslo, Montebello, N 0310 Oslo, Norway
Mol Biol Cell 17:3989-4001. 2006..This is consistent with the possibility that Fab1 functions at a late stage in endocytic receptor trafficking, at a point when signal termination has occurred...
A tumor-associated mutation of FYVE-CENT prevents its interaction with Beclin 1 and interferes with cytokinesisAntonia P Sagona
Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway
PLoS ONE 6:e17086. 2011..These findings suggest a positive feedback loop for recruitment of FYVE-CENT and Beclin 1 to the intercellular bridge during cytokinesis, and reveal a novel potential tumor suppressor mechanism for Beclin 1...
The PI 3-kinase regulator Vps15 is required for autophagic clearance of protein aggregatesKarine Lindmo
Centre for Cancer Biomedicine, University of Oslo, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, Oslo, Norway
Autophagy 4:500-6. 2008..These results provide the first genetic evidence for a function of Vps15 in autophagy in multicellular organisms and suggest that the Vps15-containing PI 3-kinase complex may play an important role in clearance of protein aggregates...
Ubiquitylation of the gap junction protein connexin-43 signals its trafficking from early endosomes to lysosomes in a process mediated by Hrs and Tsg101Edward Leithe
Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo and Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Montebello, Oslo, Norway
J Cell Sci 122:3883-93. 2009..Collectively, these data reveal a central role of early endosomes in sorting of ubiquitylated Cx43, and identify Hrs and Tsg101 as crucial regulators of trafficking of Cx43 to lysosomes...
Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative diseaseMaria Filimonenko
Centre for Cancer Biomedicine, University of Oslo and Department of Biochemistry, The Norwegian Radium Hospital, Montebello, N 0310 Oslo, Norway
J Cell Biol 179:485-500. 2007..Together, our data indicate that efficient autophagic degradation requires functional MVBs and provide a possible explanation to the observed neurodegenerative phenotype seen in patients with CHMP2B mutations...
Cloning and subcellular localization of a human phosphatidylinositol 3-phosphate 5-kinase, PIKfyve/Fab1Alicia Cabezas
Department of Biochemistry, The Norwegian Radium Hospital, Montebello, N 0310 Oslo, Norway
Gene 371:34-41. 2006..We show that PIKfyve is distributed in microdomains that are distinct from those occupied by EEA1 and Hrs...
Time-resolved ultrastructural detection of phosphatidylinositol 3-phosphateSusanne Stuffers
Dept of Biochemistry, Institute for Cancer Research, the Norwegian Radium Hospital and Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Montebello, Oslo, Norway
J Histochem Cytochem 58:1025-32. 2010..We conclude that the dimerizer-inducible probe is useful for the time-resolved detection of PtdIns(3)P at the ultrastructural level, but its effects on endosome morphology after EGF stimulation need to be taken into account...
ESCRT proteins in physiology and diseaseSusanne Stuffers
Centre for Cancer Biomedicine, Faculty Division, The Norwegian Radium Hospital, University of Oslo, Norway
Exp Cell Res 315:1619-26. 2009..We also review the additional functions of ESCRT proteins in cytokinesis and discuss how these may be related to ESCRT-associated pathologies...
Cindr interacts with anillin to control cytokinesis in Drosophila melanogasterKaisa Haglund
Department of Biochemistry, Institute for Cancer Research, Oslo University Hospital, N 0310 Oslo, Norway
Curr Biol 20:944-50. 2010..We propose that Cindr and Anillin cooperate to promote intercellular bridge stability during incomplete cytokinesis in Drosophila melanogaster...
The structure of an endosomal protein sorterThomas Slagsvold
Department of Biochemistry, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway
Dev Cell 7:457-8. 2004..Two recent reports, one in Nature and one in this issue of Developmental Cell, reveal the crystal structure of the yeast form of ESCRT-II...
Endosomal and non-endosomal functions of ESCRT proteinsThomas Slagsvold
Department of Biochemistry, the Norwegian Radium Hospital and the University of Oslo, Montebello, N-0310 Oslo, Norway
Trends Cell Biol 16:317-26. 2006..We also discuss evidence that some ESCRT subunits have evolved additional functions that are unrelated to membrane trafficking...
How a RING finger protein and a steroid hormone control autophagyKarine Lindmo
Department of Biochemistry, the Norwegian Radium Hospital and the University of Oslo, Montebello, Oslo, Norway
Autophagy 2:321-2. 2006..In this Addendum we review these findings and provide some speculations about how Dor may control both ecdysone signalling and autolysosomal fusion...
A phosphatidylinositol 3-kinase class III sub-complex containing VPS15, VPS34, Beclin 1, UVRAG and BIF-1 regulates cytokinesis and degradative endocytic trafficSigrid B Thoresen
Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Montebello, Oslo, Norway
Exp Cell Res 316:3368-78. 2010....
Cell death during Drosophila melanogaster early oogenesis is mediated through autophagyIoannis P Nezis
Centre for Cancer Biomedicine, University of Oslo and Institute for Cancer Research, Department of Biochemistry, Rikshospitalet Radiumhospitalet HF, Montebello, Oslo, Norway
Autophagy 5:298-302. 2009..This study provides new insights into the mechanisms that regulate cell death in vivo during development...
Autophagy as a trigger for cell death: autophagic degradation of inhibitor of apoptosis dBruce controls DNA fragmentation during late oogenesis in DrosophilaIoannis P Nezis
Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway
Autophagy 6:1214-5. 2010..These studies demonstrate that autophagic degradation of an inhibitor: of apoptosis is a novel mechanism of triggering cell death...
Ultrastructural characterization of giant endosomes induced by GTPase-deficient Rab5Catherine Sem Wegner
Department of Biochemistry, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, Oslo, Norway
Histochem Cell Biol 133:41-55. 2010..In addition, we observe defects in the sorting of the EGF receptor and the transferrin receptor through this compartment...
CISK attenuates degradation of the chemokine receptor CXCR4 via the ubiquitin ligase AIP4Thomas Slagsvold
Department of Biochemistry, the Norwegian Radium Hospital and the University of Oslo, Montebello, Oslo, Norway
EMBO J 25:3738-49. 2006..Taken together, these results reveal a critical function of CISK in specifically attenuating ubiquitin-dependent degradation of CXCR4, and provide a mechanistic link between the PI 3-kinase pathway and CXCR4 stability...
Regulation of membrane traffic by phosphoinositide 3-kinasesKarine Lindmo
Department of Biochemistry, Norwegian Radium Hospital and University of Oslo, Montebello, N 0310 Oslo, Norway
J Cell Sci 119:605-14. 2006..By contrast, class III PI 3-kinases mainly mediate receptor-independent trafficking events, which mostly are related to endocytic membrane traffic, phagosome maturation and autophagy...
ESCRTsLene Malerød
Department of Biochemistry, Institute for Cancer Research, Norwegian Radium Hospital, Montebello, N 0310 Oslo, Norway
Curr Biol 17:R42-3. 2007
The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteinsCamilla Raiborg
Centre for Cancer Biomedicine, Norwegian Radium Hospital, University of Oslo, Oslo, Norway
Nature 458:445-52. 2009..The involvement of the ESCRT machinery in suppressing diseases such as cancer, neurodegeneration and infections underscores its importance to the cell...
Analyzing phosphoinositides and their interacting proteinsTor Erik Rusten
Department of Biochemistry, the Norwegian Radium Hospital and the University of Oslo, Montebello, N-0310 Oslo, Norway
Nat Methods 3:251-8. 2006..Here we describe strategies and techniques for quantitative and qualitative measurement of PIs, for characterization of specific PI-binding proteins and for determination of PI kinase and phosphatase activities in vitro and in vivo...
A new side to ubiquitinCamilla Raiborg
Department of Biochemistry, the Norwegian Radium Hospital and the University of Oslo, Montebello, N-0310 Oslo, Norway
Trends Biochem Sci 31:541-4. 2006..The discovery of an alternative interaction face of ubiquitin opens new avenues for understanding how this small protein regulates protein function...
Cytokinesis and cancerAntonia P Sagona
Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway
FEBS Lett 584:2652-61. 2010..In this minireview, we will discuss the possible links between cytokinesis and cancer, and highlight key mechanisms that connect these processes...
The PtdIns3P-binding protein Phafin 2 mediates epidermal growth factor receptor degradation by promoting endosome fusionNina Marie Pedersen
Department of Biochemistry, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Montebello, N 0310, Oslo, Norway
Traffic 13:1547-63. 2012..Our results suggest that Phafin2 controls receptor trafficking and fluid-phase transport through early endosomes by facilitating endosome fusion in concert with EEA1...
Divide and ProsPer: the emerging role of PtdIns3P in cytokinesisIoannis P Nezis
Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Montebello, Oslo, Norway
Trends Cell Biol 20:642-9. 2010..Elucidating the role of PtdIns3P in cytokinesis might contribute to insight into mechanisms of tumour development and suppression...
Self-eating from an ER-associated cupAnne Simonsen
Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway
J Cell Biol 182:621-2. 2008..Griffiths, and N.T. Ktistakis. 2008. J. Cell Biol. 182:685-701) provides evidence that cup-shaped protrusions from the endoplasmic reticulum, named omegasomes, serve as platforms for autophagosome biogenesis in mammalian cells...
Alfy, a novel FYVE-domain-containing protein associated with protein granules and autophagic membranesAnne Simonsen
Department of Biochemistry, The Norwegian Radium Hospital, Montebello, Oslo 0310, Norway
J Cell Sci 117:4239-51. 2004..By electron microscopy, similar structures can be found within autophagosomes. We propose that Alfy might target cytosolic protein aggregates for autophagic degradation...
Rab GTPases as coordinators of vesicle trafficHarald Stenmark
Department of Biochemistry, Institute for Cancer Research, The Norwegian Radium Hospital, University of Oslo, Montebello, N 0310 Oslo, Norway
Nat Rev Mol Cell Biol 10:513-25. 2009..Functional impairments of Rab pathways are associated with diseases, such as immunodeficiencies, cancer and neurological disorders...
p62, an autophagy hero or culprit?Tor Erik Rusten
Centre for Cancer Biomedicine, University of Oslo and Department of Biochemistry, The Norwegian Radium Hospital Montebello, N 0310, Oslo, Norway
Nat Cell Biol 12:207-9. 2010..Lack of autophagy leads to accumulation of p62, which is not good for liver cells, as it induces a cellular stress response that leads to disease...
Programmed autophagy in the Drosophila fat body is induced by ecdysone through regulation of the PI3K pathwayTor Erik Rusten
Department of Biochemistry, The Norwegian Radium Hospital, Montebello, N 0310 Oslo
Dev Cell 7:179-92. 2004..Hence, these studies link hormonal induction of autophagy to the regulatory function of the PI3K signaling pathway in vivo...
Aberrant receptor signaling and trafficking as mechanisms in oncogenesisKaisa Haglund
Centre for Cancer Biomedicine, University of Oslo, and Department of Biochemistry, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway
Crit Rev Oncog 13:39-74. 2007..In this review we will discuss these signaling pathways and how their dysfunction may contribute to oncogenesis. We will also highlight the important role of endocytic membrane trafficking in receptor signaling and tumor suppression...
Structure and functions of stable intercellular bridges formed by incomplete cytokinesis during developmentKaisa Haglund
Department of Biochemistry Institute for Cancer Research Oslo University Hospital Centre for Cancer Biomedicine Faculty of Medicine University of Oslo Montebello, Oslo, Norway
Commun Integr Biol 4:1-9. 2011....
Cell differentiation: midbody remnants - junk or fate factors?Kay O Schink
Department of Biochemistry, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N 0310 Oslo, Norway
Curr Biol 21:R958-60. 2011..This structure has been regarded as a piece of cellular debris, but two recent papers suggest an unexpected function for the midbody remnant in promoting an undifferentiated cellular phenotype...
The ESCRT machinery mediates polarization of fibroblasts through regulation of myosin light chainViola Hélène Lobert
Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Oslo, Norway
J Cell Sci 125:29-36. 2012..These results suggest that, through their role in regulating integrin trafficking, ESCRTs regulate phosphorylation of MRLC and, subsequently, Golgi orientation and cell spreading...
Nedd4-dependent lysine-11-linked polyubiquitination of the tumour suppressor Beclin 1Harald W Platta
Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Montebello, 0310 Oslo, Norway
Biochem J 441:399-406. 2012..Beclin 1 is thus the first tumour suppressor reported to be controlled by Lys11-linked polyubiquitination...
The growth-regulatory protein HCRP1/hVps37A is a subunit of mammalian ESCRT-I and mediates receptor down-regulationKristi G Bache
Department of Biochemistry, The Norwegian Radium Hospital, Montebello, N 0310 Oslo, Norway
Mol Biol Cell 15:4337-46. 2004..Together, these results indicate that HCRP1 is a subunit of mammalian ESCRT-I and that its function is essential for lysosomal sorting of EGF receptors...
Cell biology. A helix for the final cutCamilla Raiborg
Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Montebello, Oslo, Norway
Science 331:1533-4. 2011..The constriction of a protein helix and the action of a microtubule-severing enzyme trigger the final stage of separation during cell division...
Hrs regulates multivesicular body formation via ESCRT recruitment to endosomesKristi G Bache
Department of Biochemistry, The Norwegian Radium Hospital, Montebello, N 0310 Oslo, Norway
J Cell Biol 162:435-42. 2003..We conclude that Hrs mediates the initial recruitment of ESCRT-I to endosomes and, thereby, indirectly regulates multivesicular body formation...
Phosphatidylinositol 3-phosphate is found in microdomains of early endosomesDavid J Gillooly
Department of Biochemistry, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway
Histochem Cell Biol 120:445-53. 2003..These microdomains may be necessary for the assembly of distinct multimolecular complexes that specify organelle identity, membrane trafficking and receptor signalling...
Working out coupled monoubiquitinationKaisa Haglund
Nat Cell Biol 8:1218-9. 2006
The mammalian phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) regulates endosome-to-TGN retrograde transportAnna C Rutherford
The Henry Wellcome Integrated Signalling Laboratories, Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol, BS8 1TD, UK
J Cell Sci 119:3944-57. 2006..It follows that the swollen endosomal phenotype observed in PIKfyve-suppressed cells results primarily from a reduction in retrograde membrane fission rather than a defect in multivesicular body biogenesis...
Cell-cycle-dependent binding kinetics for the early endosomal tethering factor EEA1Trygve Bergeland
Department of Molecular Biosciences, University of Oslo, PO Box 1041, Blindernveien 31, Oslo 0316, Norway
EMBO Rep 9:171-8. 2008..This might be a general mechanism to fine-tune and control tethering and fusion of early endosomes...
Role of Rab5 in the recruitment of hVps34/p150 to the early endosomeJames T Murray
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA
Traffic 3:416-27. 2002..However, Rab5 does not appear to act by directly recruiting p150/hVps34 complexes from the cytosol to the endosomal membrane...
Double-sided ubiquitin binding of Hrs-UIM in endosomal protein sortingSatoshi Hirano
Structural Biology Research Center, Photon Factory, Institute of Materials Structure Science, High Energy Accelerator Research Organization, Tsukuba, Ibaraki 305 0801, Japan
Nat Struct Mol Biol 13:272-7. 2006..Hrs-UIM belongs to a new subclass of double-sided UIMs, in contrast to its yeast homolog Vps27p, which has two tandem single-sided UIMs...
The biogenesis of multivesicular endosomesJean Gruenberg
Department of Biochemistry, University of Geneva, 30 Quai Ernest Ansermet, 1211-Geneva-4, Switzerland
Nat Rev Mol Cell Biol 5:317-23. 2004
Regulation of ubiquitin-binding proteins by monoubiquitinationDaniela Hoeller
Institute for Biochemistry II, Goethe University Medical School, Theodor Stern Kai 7, 60590 Frankfurt, Germany
Nat Cell Biol 8:163-9. 2006..We propose that monoubiquitination of ubiquitin-binding proteins inhibits their capacity to bind to and control the functions of ubiquitinated targets in vivo...
Modulation of receptor recycling and degradation by the endosomal kinesin KIF16BSebastian Hoepfner
Max Planck Institute for Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, D 01307 Dresden, Germany
Cell 121:437-50. 2005..We propose that this mechanism could have important implications for signaling...
Misfolding diverts CFTR from recycling to degradation: quality control at early endosomesManu Sharma
Hospital for Sick Children, Program in Cell and Lung Biology, 555 University Ave, Toronto, Ontario M5G 1X8, Canada
J Cell Biol 164:923-33. 2004....
Structural basis of ubiquitin recognition by mammalian Eap45 GLUE domainSatoshi Hirano
Structural Biology Research Center, Photon Factory, Institute of Materials Structure Science, High Energy Accelerator Research Organization KEK, Tsukuba, Ibaraki 305 0801, Japan
Nat Struct Mol Biol 13:1031-2. 2006..In the Eap45 GLUE-Ub complex structure, Ub binds far from the proposed PI-binding site of Eap45 GLUE, suggesting their independent binding...
