MARC WALLACE KIRSCHNER

Summary

Affiliation: Harvard University
Country: USA

Publications

  1. pmc The roles of APC and Axin derived from experimental and theoretical analysis of the Wnt pathway
    Ethan Lee
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA
    PLoS Biol 1:E10. 2003
  2. pmc Evolvability
    M Kirschner
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 95:8420-7. 1998
  3. ncbi request reprint Intracellular proteolysis
    M Kirschner
    Dept of Cell Biology, Harvard Medical School, Boston, MA, USA
    Trends Cell Biol 9:M42-5. 1999
  4. doi request reprint Profile: Bruce Alberts, Science's new editor
    Marc Kirschner
    Harvard Medical School, Boston, MA 02215, USA
    Science 319:1199. 2008
  5. ncbi request reprint The meaning of systems biology
    Marc W Kirschner
    Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell 121:503-4. 2005
  6. ncbi request reprint Drosophila genome-scale screen for PAN GU kinase substrates identifies Mat89Bb as a cell cycle regulator
    Laura A Lee
    Whitehead Institute, Cambridge, Massachusetts 02142, USA
    Dev Cell 8:435-42. 2005
  7. pmc Stable isotope-free relative and absolute quantitation of protein phosphorylation stoichiometry by MS
    Hanno Steen
    Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:3948-53. 2005
  8. ncbi request reprint Sororin, a substrate of the anaphase-promoting complex, is required for sister chromatid cohesion in vertebrates
    Susannah Rankin
    Systems Biology Department, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 18:185-200. 2005
  9. ncbi request reprint Phosphorylation analysis by mass spectrometry: myths, facts, and the consequences for qualitative and quantitative measurements
    Hanno Steen
    Department of Pathology, Harvard Medical School and Children s Hospital, Boston, Massachusetts 02115, USA
    Mol Cell Proteomics 5:172-81. 2006
  10. ncbi request reprint Identification of ubiquitin ligase substrates by in vitro expression cloning
    Nagi G Ayad
    Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA
    Methods Enzymol 399:404-14. 2005

Research Grants

  1. BIOCHEMICAL STUDIES OF MITOSIS
    MARC WALLACE KIRSCHNER; Fiscal Year: 2011
  2. CELL CYCLE REGULATION
    Marc Kirschner; Fiscal Year: 2004
  3. BIOCHEMICAL STUDIES OF MITOSIS
    Marc Kirschner; Fiscal Year: 2007
  4. CELL CYCLE REGULATION
    MARC WALLACE KIRSCHNER; Fiscal Year: 2010
  5. BIOCHEMICAL STUDIES OF MITOSIS
    MARC WALLACE KIRSCHNER; Fiscal Year: 2010
  6. CELL CYCLE REGULATION
    Marc Kirschner; Fiscal Year: 2007
  7. DEVELOPMENTAL CIRCUITS IN GASTRULATION AND NEURULATION
    Marc Kirschner; Fiscal Year: 2007
  8. DEVELOPMENTAL CIRCUITS IN GASTRULATION AND NEURULATION
    Marc Kirschner; Fiscal Year: 2003
  9. BIOCHEMICAL STUDIES OF MITOSIS
    Marc Kirschner; Fiscal Year: 1999
  10. BIOCHEMICAL STUDIES OF MITOSIS
    Marc Kirschner; Fiscal Year: 2003

Collaborators

Detail Information

Publications38

  1. pmc The roles of APC and Axin derived from experimental and theoretical analysis of the Wnt pathway
    Ethan Lee
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA
    PLoS Biol 1:E10. 2003
    ..By applying control analysis to our mathematical model, we demonstrate the modular design, sensitivity, and robustness of the Wnt pathway and derive an explicit expression for tumor suppression and oncogenicity...
  2. pmc Evolvability
    M Kirschner
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 95:8420-7. 1998
    ..Evolvability may have been generally selected in the course of selection for robust, flexible processes suitable for complex development and physiology and specifically selected in lineages undergoing repeated radiations...
  3. ncbi request reprint Intracellular proteolysis
    M Kirschner
    Dept of Cell Biology, Harvard Medical School, Boston, MA, USA
    Trends Cell Biol 9:M42-5. 1999
    ..In this review, I attempt to trace the curious history of intracellular protein degradation, its novel and elegant biochemistry and to extract the features that might be important for the next era of studies in cell physiology...
  4. doi request reprint Profile: Bruce Alberts, Science's new editor
    Marc Kirschner
    Harvard Medical School, Boston, MA 02215, USA
    Science 319:1199. 2008
  5. ncbi request reprint The meaning of systems biology
    Marc W Kirschner
    Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell 121:503-4. 2005
  6. ncbi request reprint Drosophila genome-scale screen for PAN GU kinase substrates identifies Mat89Bb as a cell cycle regulator
    Laura A Lee
    Whitehead Institute, Cambridge, Massachusetts 02142, USA
    Dev Cell 8:435-42. 2005
    ..Thus, Mat89Bb plays an evolutionarily conserved role as a crucial regulator of both cell cycle and development...
  7. pmc Stable isotope-free relative and absolute quantitation of protein phosphorylation stoichiometry by MS
    Hanno Steen
    Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 102:3948-53. 2005
    ..These approaches were validated and subsequently applied to the phosphorylation of the yeast transcription factor Pho4...
  8. ncbi request reprint Sororin, a substrate of the anaphase-promoting complex, is required for sister chromatid cohesion in vertebrates
    Susannah Rankin
    Systems Biology Department, Harvard Medical School, Boston, Massachusetts 02115, USA
    Mol Cell 18:185-200. 2005
    ..We speculate that the protein, which we have named sororin, regulates the ability of the cohesin complex to mediate sister chromatid cohesion, perhaps by altering the nature of the interaction of cohesin with the chromosomes...
  9. ncbi request reprint Phosphorylation analysis by mass spectrometry: myths, facts, and the consequences for qualitative and quantitative measurements
    Hanno Steen
    Department of Pathology, Harvard Medical School and Children s Hospital, Boston, Massachusetts 02115, USA
    Mol Cell Proteomics 5:172-81. 2006
    ....
  10. ncbi request reprint Identification of ubiquitin ligase substrates by in vitro expression cloning
    Nagi G Ayad
    Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA
    Methods Enzymol 399:404-14. 2005
    ..All these considerations have motivated a search for other techniques to assist in identifying substrates of this particular E3 ligase. Here, we describe the use of in vitro expression cloning to identify novel APC substrates...
  11. ncbi request reprint The processivity of multiubiquitination by the APC determines the order of substrate degradation
    Michael Rape
    Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell 124:89-103. 2006
    ..The processivity of multiubiquitination is strongly influenced by the D box within the substrate, suggesting that substrate ordering is established by a mechanism intrinsic to APC and its substrates and similar to kinetic proofreading...
  12. ncbi request reprint Obituary: Reinhart Heinrich (1946-2006)
    Marc W Kirschner
    Marc W Kirschner is at Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 444:700. 2006
  13. ncbi request reprint Regulation of Cdc25C by ERK-MAP kinases during the G2/M transition
    Ruoning Wang
    Department of Experimental Therapeutics, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Cell 128:1119-32. 2007
    ..Inhibition of ERK activation partially inhibits T48 phosphorylation, Cdc25C activation, and mitotic induction. These findings demonstrate that ERK-MAP kinases are directly involved in activating Cdc25 during the G(2)/M transition...
  14. ncbi request reprint Anaphase initiation is regulated by antagonistic ubiquitination and deubiquitination activities
    Frank Stegmeier
    Howard Hughes Medical Institute, Department of Genetics, Harvard Partners Center for Genetics and Genomics, Boston, Massachusetts 02115, USA
    Nature 446:876-81. 2007
    ....
  15. ncbi request reprint Autonomous regulation of the anaphase-promoting complex couples mitosis to S-phase entry
    Michael Rape
    Department of Systems Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nature 432:588-95. 2004
    ..This indicates that the core of the metazoan cell cycle could be described as a self-perpetuating but highly regulated oscillator composed of alternating CDK and APC activities...
  16. pmc Purification and architecture of the ubiquitous Wave complex
    Alexis Gautreau
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 101:4379-83. 2004
    ..The complex is organized around a core of Nap and Abi. Sra is a peripheral subunit recruited on the Nap side, whereas the Wave and Hspc subunits are recruited on the Abi side of the core...
  17. pmc Different phosphorylation states of the anaphase promoting complex in response to antimitotic drugs: a quantitative proteomic analysis
    Judith A J Steen
    Departments of Neurobiology and Pathology, Harvard Medical School and Children s Hospital Boston, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 105:6069-74. 2008
    ..We discuss these findings in terms of the variable efficacy of antimitotic drugs in cancer chemotherapy...
  18. pmc Mouse ribonucleotide reductase R2 protein: a new target for anaphase-promoting complex-Cdh1-mediated proteolysis
    Anna Lena Chabes
    Department of Medical Biochemistry and Biophysics, Umea University, SE 901 87 Umea, Sweden
    Proc Natl Acad Sci U S A 100:3925-9. 2003
    ..The newly discovered p53-induced p53R2 protein that lacks a KEN box may supply deoxyribonucleotides for DNA repair during G(0)G(1)...
  19. ncbi request reprint Tome-1, a trigger of mitotic entry, is degraded during G1 via the APC
    Nagi G Ayad
    Department of Cell Biology, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA
    Cell 113:101-13. 2003
    ..Degradation of Tome-1 during G1 allows for wee 1 accumulation during interphase, thereby providing a critical link between the APC and SCF pathways in regulation of cdk1/cyclin B activity and thus mitotic entry and exit...
  20. pmc Absolute quantification of proteins and phosphoproteins from cell lysates by tandem MS
    Scott A Gerber
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 100:6940-5. 2003
    ..The methods described here represent focused, alternative approaches for studying the dynamically changing proteome...
  21. ncbi request reprint Anaphase specific auto-cleavage of separase
    Hui Zou
    Department of Molecular Biology, UT Southwestern Medical Center at Dallas, 75390, USA
    FEBS Lett 528:246-50. 2002
    ..The cleaved fragments remain associated with each other and are catalytically active. Mapping of the cleavage sites reveals that all three sites are conserved in vertebrates underlining a significant function for this regulation...
  22. pmc Clustering of Nck by a 12-residue Tir phosphopeptide is sufficient to trigger localized actin assembly
    Kenneth G Campellone
    Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, 55 Lake Ave North, Worcester, MA 01655, USA
    J Cell Biol 164:407-16. 2004
    ..Consistent with this finding, clustering of Nck by a 12-residue Tir phosphopeptide triggered actin tail formation in Xenopus egg extracts...
  23. ncbi request reprint Degradation of the SCF component Skp2 in cell-cycle phase G1 by the anaphase-promoting complex
    Wenyi Wei
    Department of Medical Oncology, Dana Farber Cancer Institute and Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Nature 428:194-8. 2004
    ..As a result, accumulation of SCF(SKP2) requires prior inactivation of APC(CDH1). These findings provide an insight into the orchestration of SCF and APC activities during cell-cycle progression, and into the involvement of the APC in G1...
  24. ncbi request reprint Timing of events in mitosis
    Ann B Georgi
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Curr Biol 12:105-14. 2002
    ....
  25. ncbi request reprint Cyclin B and E2F-1 expression in prostate carcinoma cells treated with the novel retinoid CD437 are regulated by the ubiquitin-mediated pathway
    Lulu Farhana
    John D Dingell VA Medical Center and Karmanos Cancer Institute, and Department Internal Medicine, Wayne State University, Detroit, Michigan 48201, USA
    Cancer Res 62:3842-9. 2002
    ..Thus, CD437 modulates the expression of E2F-1 and cyclin B through the simultaneous stimulation and inhibition of the cyclin B and E2F-1 E3 ligases, respectively...
  26. ncbi request reprint A novel set of Wnt-Frizzled fusion proteins identifies receptor components that activate beta -catenin-dependent signaling
    Sheri L Holmen
    Laboratory of Cell Signaling and Carcinogenesis, Van Andel Research Institute, Grand Rapids, Michigan 49503, USA
    J Biol Chem 277:34727-35. 2002
    ..The data suggest that the distinction between the two Wnt classes lies not in intrinsic differences in the molecules but via the Frizzled molecules with which they interact...
  27. ncbi request reprint The Drosophila homolog of MCPH1, a human microcephaly gene, is required for genomic stability in the early embryo
    Jamie L Rickmyre
    Department of Cell and Developmental Biology, Vanderbilt University Medical Center, U 4200 MRBIII, 465 21st Avenue South, Nashville, TN 37232 8240, USA
    J Cell Sci 120:3565-77. 2007
    ..Finally, brains of mcph1 adult male flies have defects in mushroom body structure, suggesting an evolutionarily conserved role for MCPH1 in brain development...
  28. pmc The relationship between evolutionary and physiological variation in hemoglobin
    Ron Milo
    Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 104:16998-7003. 2007
    ..This orthogonality suggests continued selection for physiological adaptability and hints at a role for this adaptability in evolutionary change...
  29. pmc Biochemical suppression of small-molecule inhibitors: a strategy to identify inhibitor targets and signaling pathway components
    Jeffrey R Peterson
    Division of Basic Sciences, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, Pennsylvania 19111, USA
    Chem Biol 13:443-52. 2006
    ..This work introduces a general method for using low-micromolar chemical inhibitors to identify both inhibitor targets and other components of a signaling pathway...
  30. ncbi request reprint In vitro reconstitution of cdc42-mediated actin assembly using purified components
    Hsin Yi Henry Ho
    Division of Neuroscience, Children s Hospital, Boston, MA, USA
    Methods Enzymol 406:174-90. 2006
    ..In this chapter, we describe the preparation of the components used in these purified actin assembly reactions, as well as the assay conditions under which we monitor actin polymerization kinetics in vitro...
  31. ncbi request reprint Cdc42 and PI(4,5)P2-induced actin assembly in Xenopus egg extracts
    Andres M Lebensohn
    Harvard Medical School, Boston, MA, USA
    Methods Enzymol 406:156-73. 2006
    ..Finally we provide a protocol for immunodepletion of proteins and discuss the use of immunodepletion and rescue experiments for functional analysis of components in the extracts...
  32. pmc Hem-1 complexes are essential for Rac activation, actin polymerization, and myosin regulation during neutrophil chemotaxis
    Orion D Weiner
    Department of Systems Biology, Harvard Medical School, Boston, Massachusetts, USA
    PLoS Biol 4:e38. 2006
    ....
  33. ncbi request reprint The secreted Frizzled-related protein Sizzled functions as a negative feedback regulator of extreme ventral mesoderm
    Licio Collavin
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Development 130:805-16. 2003
    ..Our data are consistent with the existence of some limited self-organizing properties of the extreme ventral mesoderm...
  34. ncbi request reprint Xbra functions as a switch between cell migration and convergent extension in the Xenopus gastrula
    Kristen M Kwan
    Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
    Development 130:1961-72. 2003
    ..In addition, Xbra appears to inhibit cell migration by inhibiting adhesion to fibronectin. We propose that Xbra functions as a switch to keep cell migration and convergent extension as mutually exclusive behaviors during gastrulation...
  35. ncbi request reprint Domain structure of separase and its binding to securin as determined by EM
    Hector Viadiu
    Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA
    Nat Struct Mol Biol 12:552-3. 2005
    ..Based on labeling data and sequence analysis, we propose a model for the structure of separase, consisting of 26 ARM repeats, an unstructured region of 280 residues and two caspase-like domains, with securin binding to the ARM repeats...
  36. ncbi request reprint The tumour suppressor RASSF1A regulates mitosis by inhibiting the APC-Cdc20 complex
    Min Sup Song
    Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 373 1 Guseoung D, Yuseong G, Daejeon 305 701, Korea
    Nat Cell Biol 6:129-37. 2004
    ..It also caused a cell division defect characterized by centrosome abnormalities and multipolar spindles. These findings implicate RASSF1A in the regulation of both APC-Cdc20 activity and mitotic progression...
  37. ncbi request reprint Toca-1 mediates Cdc42-dependent actin nucleation by activating the N-WASP-WIP complex
    Hsin Yi Henry Ho
    Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA
    Cell 118:203-16. 2004
    ..These findings represent a significantly revised view of Cdc42-signaling and shed light on the pathogenesis of Wiskott-Aldrich syndrome...
  38. pmc Erk/Src phosphorylation of cortactin acts as a switch on-switch off mechanism that controls its ability to activate N-WASP
    Narcisa Martinez-Quiles
    Division of Immunology, Children s Hospital, Boston, MA 02115, USA
    Mol Cell Biol 24:5269-80. 2004
    ....

Research Grants45

  1. BIOCHEMICAL STUDIES OF MITOSIS
    MARC WALLACE KIRSCHNER; Fiscal Year: 2011
    ..Control of cell growth and cell shape are both fundamental to understanding many pathological conditions, in cancer and embryology. ..
  2. CELL CYCLE REGULATION
    Marc Kirschner; Fiscal Year: 2004
    ..We ask how APC recognizes substrates and temporally distinguishes among them. Finally we examine the diversity of APC regulators and begin to characterize the possible role of APC outside the cell cycle. ..
  3. BIOCHEMICAL STUDIES OF MITOSIS
    Marc Kirschner; Fiscal Year: 2007
    ..These studies are aimed at understanding actin regulation in a cellular context and the integration of actin regulation with other cellular functions. ..
  4. CELL CYCLE REGULATION
    MARC WALLACE KIRSCHNER; Fiscal Year: 2010
    ..As such, it is a promising target for pharmacologic intervention. This proposal studies which proteins are signaled out for regulated degradation and on a molecular level how the particular choices are made. ..
  5. BIOCHEMICAL STUDIES OF MITOSIS
    MARC WALLACE KIRSCHNER; Fiscal Year: 2010
    ..Control of cell growth and cell shape are both fundamental to understanding many pathological conditions, in cancer and embryology. ..
  6. CELL CYCLE REGULATION
    Marc Kirschner; Fiscal Year: 2007
    ..Finally we propose to study two APC substrates with important biological effects: one involved in chromatid cohesion and the other affecting the growth of the brain in a human genetic disease. ..
  7. DEVELOPMENTAL CIRCUITS IN GASTRULATION AND NEURULATION
    Marc Kirschner; Fiscal Year: 2007
    ..Our major approach here is to examine the early embryology of the acorn worm, Saccoglossus kowalevskii, and identify genes which in vertebrates play a major role in the Organizer. ..
  8. DEVELOPMENTAL CIRCUITS IN GASTRULATION AND NEURULATION
    Marc Kirschner; Fiscal Year: 2003
    ..In the process, we will be investigating signaling pathways that may be use in many contexts of human biology. ..
  9. BIOCHEMICAL STUDIES OF MITOSIS
    Marc Kirschner; Fiscal Year: 1999
    ..In aim 6 the activation of cdc2 by cyclin B and the identity and role of other activators and inhibitors will be studied. ..
  10. BIOCHEMICAL STUDIES OF MITOSIS
    Marc Kirschner; Fiscal Year: 2003
    ..Specifically we will also be looking for clues for its role in generating aneuploidy and the reasons why it is oncogenic. ..
  11. CELL CYCLE REGULATION
    Marc Kirschner; Fiscal Year: 2000
    ..Following experiments on the vertebrate homolog of cdc34, we plan to characterize its pathway of ubiquitin mediated degradation and potential substrates relative to the onset of DNA replication. ..