DF/HCC Program Affiliation

Cancer Cell Biology

Research Abstract

My research concerns the regulation of the cell cycle, the nature of hte cytoskeleton, and mechanisms of early vertebrate development. In particular we are concerned with the role of proteolysis in the exit from mitosis and the checkpoint mechanisms at work there. We are also concerned with the role of proteolysis during the G1 period. We have used Xenopus eggs and extracts to dissect these mechanisms biochemically. In addition we have been interested in understanding how actin assembly is regulated by signal transduction mechanisms. Finally, we are trying to understand the early signaling and patterning events of the frog embryo and how these events lead to the establishment of the vertebrate body plan.

Publications

• Stegmeier F, Rape M, Draviam VM, Nalepa G, Sowa ME, Ang XL, McDonald ER, Li MZ, Hannon GJ, Sorger PK, Kirschner MW, Harper JW, Elledge SJ.Anaphase initiation is regulated by antagonistic ubiquitination and deubiquitination activities.Nature 2007 Apr 19;44
  17443180
• Zou H, McGarry TJ, Bernal T, Kirschner MW.Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis.Science 1999 Jul 16;285(5426):418-22.
  10411507
• Rohatgi R, Ma L, Miki H, Lopez M, Kirchhausen T, Takenawa T, Kirschner MW.The interaction between N-WASP and the Arp2/3 complex links Cdc42-dependent signals to actin assembly.Cell 1999 Apr 16;97(2):221-31.
  10219243
• Fang G, Yu H, Kirschner MW.Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1.Mol Cell 1998 Aug;2(2):163-71.
  9734353
• Steen JA, Steen H, Georgi A, Parker K, Springer M, Kirchner M, Hamprecht F, Kirschner MW.Different phosphorylation states of the anaphase promoting complex in response to antimitotic drugs: a quantitative proteomic analysis.Proc Natl Acad Sci U S A 2008 A
  18420821
• Mor I, Sklan EH, Podoly E, Pick M, Kirschner M, Yogev L, Bar-Sheshet Itach S, Schreiber L, Geyer B, Mor T, Grisaru D, Soreq H.Acetylcholinesterase-R increases germ cell apoptosis but enhances sperm motility.J Cell Mol Med 2008 Mar-Apr;12(2):479-95.
  18194455
• Milo R, Hou JH, Springer M, Brenner MP, Kirschner MW.The relationship between evolutionary and physiological variation in hemoglobin.Proc Natl Acad Sci U S A 2007 Oct 23;104(43):16998-7003.
  17942680
• Weiner OD, Marganski WA, Wu LF, Altschuler SJ, Kirschner MW.An actin-based wave generator organizes cell motility.PLoS Biol 2007 Sep;5(9):e221.
  17696648
• Reddy SK, Rape M, Margansky WA, Kirschner MW.Ubiquitination by the anaphase-promoting complex drives spindle checkpoint inactivation.Nature 2007 Apr 19;446(7138):921-5.
  17443186
• Rape M, Reddy SK, Kirschner MW.The processivity of multiubiquitination by the APC determines the order of substrate degradation.Cell 2006 Jan 13;124(1):89-103.
  16413484
• Wei W, Ayad NG, Wan Y, Zhang GJ, Kirschner MW, Kaelin WG.Degradation of the SCF component Skp2 in cell-cycle phase G1 by the anaphase-promoting complex.Nature 2004 Mar 11;428(6979):194-8.
  15014503
• Yan C, Martinez-Quiles N, Eden S, Shibata T, Takeshima F, Shinkura R, Fujiwara Y, Bronson R, Snapper SB, Kirschner MW, Geha R, Rosen FS, Alt FW.WAVE2 deficiency reveals distinct roles in embryogenesis and Rac-mediated actin-based motility.EMBO J 2003 Jul
  12853475
• Peterson JR, Lokey RS, Mitchison TJ, Kirschner MW.A chemical inhibitor of N-WASP reveals a new mechanism for targeting protein interactions.Proc Natl Acad Sci U S A 2001 Sep 11;98(19):10624-9.
  11553809
• Ma L, Rohatgi R, Kirschner MW.The Arp2/3 complex mediates actin polymerization induced by the small GTP-binding protein Cdc42.Proc Natl Acad Sci U S A 1998 Dec 22;95(26):15362-7.
  9860974
• McGarry TJ, Kirschner MW.Geminin, an inhibitor of DNA replication, is degraded during mitosis.Cell 1998 Jun 12;93(6):1043-53.
  9635433
• Fang G, Yu H, Kirschner MW.The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase initiation.Genes Dev 1998 Jun 15;12(12):1871-83.
  9637688
• King RW, Deshaies RJ, Peters JM, Kirschner MW.How proteolysis drives the cell cycle.Science 1996 Dec 6;274(5293):1652-9.
  8939846
• Lustig KD, Kroll KL, Sun EE, Kirschner MW.Expression cloning of a Xenopus T-related gene (Xombi) involved in mesodermal patterning and blastopore lip formation.Development 1996 Dec;122(12):4001-12.
  9012520
• Peters JM, King RW, Höög C, Kirschner MW.Identification of BIME as a subunit of the anaphase-promoting complex.Science 1996 Nov 15;274(5290):1199-201.
  8895470