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      Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2

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          Abstract

          The mitotic checkpoint prevents cells with unaligned chromosomes from prematurely exiting mitosis by inhibiting the anaphase-promoting complex/cyclosome (APC/C) from targeting key proteins for ubiquitin-mediated proteolysis. We have examined the mechanism by which the checkpoint inhibits the APC/C by purifying an APC/C inhibitory factor from HeLa cells. We call this factor the mitotic checkpoint complex (MCC) as it consists of hBUBR1, hBUB3, CDC20, and MAD2 checkpoint proteins in near equal stoichiometry. MCC inhibitory activity is 3,000-fold greater than that of recombinant MAD2, which has also been shown to inhibit APC/C in vitro. Surprisingly, MCC is not generated from kinetochores, as it is also present and active in interphase cells. However, only APC/C isolated from mitotic cells was sensitive to inhibition by MCC. We found that the majority of the APC/C in mitotic lysates is associated with the MCC, and this likely contributes to the lag in ubiquitin ligase activity. Importantly, chromosomes can suppress the reactivation of APC/C. Chromosomes did not affect the inhibitory activity of MCC or the stimulatory activity of CDC20. We propose that the preformed interphase pool of MCC allows for rapid inhibition of APC/C when cells enter mitosis. Unattached kinetochores then target the APC/C for sustained inhibition by the MCC.

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          Rapid planetesimal formation in turbulent circumstellar discs

          The initial stages of planet formation in circumstellar gas discs proceed via dust grains that collide and build up larger and larger bodies (Safronov 1969). How this process continues from metre-sized boulders to kilometre-scale planetesimals is a major unsolved problem (Dominik et al. 2007): boulders stick together poorly (Benz 2000), and spiral into the protostar in a few hundred orbits due to a head wind from the slower rotating gas (Weidenschilling 1977). Gravitational collapse of the solid component has been suggested to overcome this barrier (Safronov 1969, Goldreich & Ward 1973, Youdin & Shu 2002). Even low levels of turbulence, however, inhibit sedimentation of solids to a sufficiently dense midplane layer (Weidenschilling & Cuzzi 1993, Dominik et al. 2007), but turbulence must be present to explain observed gas accretion in protostellar discs (Hartmann 1998). Here we report the discovery of efficient gravitational collapse of boulders in locally overdense regions in the midplane. The boulders concentrate initially in transient high pressures in the turbulent gas (Johansen, Klahr, & Henning 2006), and these concentrations are augmented a further order of magnitude by a streaming instability (Youdin & Goodman 2005, Johansen, Henning, & Klahr 2006, Johansen & Youdin 2007) driven by the relative flow of gas and solids. We find that gravitationally bound clusters form with masses comparable to dwarf planets and containing a distribution of boulder sizes. Gravitational collapse happens much faster than radial drift, offering a possible path to planetesimal formation in accreting circumstellar discs.
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            The Dicke Quantum Phase Transition with a Superfluid Gas in an Optical Cavity

            A phase transition describes the sudden change of state in a physical system, such as the transition between a fluid and a solid. Quantum gases provide the opportunity to establish a direct link between experiment and generic models which capture the underlying physics. A fundamental concept to describe the collective matter-light interaction is the Dicke model which has been predicted to show an intriguing quantum phase transition. Here we realize the Dicke quantum phase transition in an open system formed by a Bose-Einstein condensate coupled to an optical cavity, and observe the emergence of a self-organized supersolid phase. The phase transition is driven by infinitely long-ranged interactions between the condensed atoms. These are induced by two-photon processes involving the cavity mode and a pump field. We show that the phase transition is described by the Dicke Hamiltonian, including counter-rotating coupling terms, and that the supersolid phase is associated with a spontaneously broken spatial symmetry. The boundary of the phase transition is mapped out in quantitative agreement with the Dicke model. The work opens the field of quantum gases with long-ranged interactions, and provides access to novel quantum phases.
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              A relativistic jetted outburst from a massive black hole fed by a tidally disrupted star

              While gas accretion onto some massive black holes (MBHs) at the centers of galaxies actively powers luminous emission, the vast majority of MBHs are considered dormant. Occasionally, a star passing too near a MBH is torn apart by gravitational forces, leading to a bright panchromatic tidal disruption flare (TDF). While the high-energy transient Swift J164449.3+573451 ("Sw 1644+57") initially displayed none of the theoretically anticipated (nor previously observed) TDF characteristics, we show that the observations (Levan et al. 2011) suggest a sudden accretion event onto a central MBH of mass ~10^6-10^7 solar masses. We find evidence for a mildly relativistic outflow, jet collimation, and a spectrum characterized by synchrotron and inverse Compton processes; this leads to a natural analogy of Sw 1644+57 with a smaller-scale blazar. The phenomenologically novel Sw 1644+57 thus connects the study of TDFs and active galaxies, opening a new vista on disk-jet interactions in BHs and magnetic field generation and transport in accretion systems.
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                Author and article information

                Journal
                J Cell Biol
                The Journal of Cell Biology
                The Rockefeller University Press
                0021-9525
                1540-8140
                3 September 2001
                : 154
                : 5
                : 925-936
                Affiliations
                Institute for Cancer Research, The Fox Chase Cancer Center, Philadelphia, PA 19111
                Author notes

                Address correspondence to Tim Yen, Institute for Cancer Research, The Fox Chase Cancer Center, 7701 Burholme Ave., Philadelphia, PA 19111. Tel.: (215) 728-2590. Fax: (215) 728-2412. E-mail: tj_yen@ 123456fccc.edu

                Article
                0102093
                10.1083/jcb.200102093
                2196190
                11535616
                45427357-a799-4ec8-bc77-2bd1fb3eb0dc
                Copyright © 2001, The Rockefeller University Press
                History
                : 16 February 2001
                : 11 July 2001
                : 13 July 2001
                Categories
                Article

                Cell biology
                kinetochore; hbubr1; anaphase promoting complex; mad2; mitotic checkpoint

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