DF/HCC Program Affiliation

Cancer Cell Biology

Research Abstract

My work is focused on understanding how the cell division cycle is controlled. We study the regulation of cyclin-dependent kinases and their inhibitors as well as other signalling pathways controlled by protein kinases. Much of this regulation occurs through protein turnover through the ubiquitin pathway. My lab is interested in the control of protein turnover through the SCF ubiquitin ligases. In recent years, we have identified ubiquitin ligases for I-kappa B, beta-catenin, cyclin E, and Cdc25, key regulators of cell division and survival. Currently, genomic and biochemical approaches are being used to dissect how that activities of these and other processes are controlled.

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
• Draviam VM, Stegmeier F, Nalepa G, Sowa ME, Chen J, Liang A, Hannon GJ, Sorger PK, Harper JW, Elledge SJ.A functional genomic screen identifies a role for TAO1 kinase in spindle-checkpoint signalling.Nat Cell Biol 2007 May;9(5):556-64.
  17417629
• Sundqvist A, Bengoechea-Alonso MT, Ye X, Lukiyanchuk V, Jin J, Harper JW, Ericsson J.Control of lipid metabolism by phosphorylation-dependent degradation of the SREBP family of transcription factors by SCF(Fbw7).Cell Metab 2005 Jun;1(6):379-91.
  16054087
• Wei W, Jin J, Schlisio S, Harper JW, Kaelin WG.The v-Jun point mutation allows c-Jun to escape GSK3-dependent recognition and destruction by the Fbw7 ubiquitin ligase.Cancer Cell 2005 Jul;8(1):25-33.
  16023596
• Jin J, Shirogane T, Xu L, Nalepa G, Qin J, Elledge SJ, Harper JW.SCFbeta-TRCP links Chk1 signaling to degradation of the Cdc25A protein phosphatase.Genes Dev 2003 Dec 15;17(24):3062-74.
  14681206
• Ye X, Wei Y, Nalepa G, Harper JW.The cyclin E/Cdk2 substrate p220(NPAT) is required for S-phase entry, histone gene expression, and Cajal body maintenance in human somatic cells.Mol Cell Biol 2003 Dec;23(23):8586-600.
  14612403
• Xu L, Wei Y, Reboul J, Vaglio P, Shin TH, Vidal M, Elledge SJ, Harper JW.BTB proteins are substrate-specific adaptors in an SCF-like modular ubiquitin ligase containing CUL-3.Nature 2003 Sep 18;425(6955):316-21.
  13679922
• Wu G, Xu G, Schulman BA, Jeffrey PD, Harper JW, Pavletich NP.Structure of a beta-TrCP1-Skp1-beta-catenin complex: destruction motif binding and lysine specificity of the SCF(beta-TrCP1) ubiquitin ligase.Mol Cell 2003 Jun;11(6):1445-56.
  12820959
• Wang Y, Shirogane T, Liu D, Harper JW, Elledge SJ.Exit from exit: resetting the cell cycle through Amn1 inhibition of G protein signaling.Cell 2003 Mar 7;112(5):697-709.
  12628189