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Lee Tzumin Lab / Publications
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5 Publications

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    Tjian Lab
    08/15/03 | Control of cell number by Drosophila FOXO: downstream and feedback regulation of the insulin receptor pathway.
    Puig O, Marr MT, Ruhf ML, Tjian R
    Genes & Development. 2003 Aug 15;17(16):2006-20. doi: 10.1073/pnas.1100640108

    The Drosophila insulin receptor (dInR) regulates cell growth and proliferation through the dPI3K/dAkt pathway, which is conserved in metazoan organisms. Here we report the identification and functional characterization of the Drosophila forkhead-related transcription factor dFOXO, a key component of the insulin signaling cascade. dFOXO is phosphorylated by dAkt upon insulin treatment, leading to cytoplasmic retention and inhibition of its transcriptional activity. Mutant dFOXO lacking dAkt phosphorylation sites no longer responds to insulin inhibition, remains in the nucleus, and is constitutively active. dFOXO activation in S2 cells induces growth arrest and activates two key players of the dInR/dPI3K/dAkt pathway: the translational regulator d4EBP and the dInR itself. Induction of d4EBP likely leads to growth inhibition by dFOXO, whereas activation of dInR provides a novel transcriptionally induced feedback control mechanism. Targeted expression of dFOXO in fly tissues regulates organ size by specifying cell number with no effect on cell size. Our results establish dFOXO as a key transcriptional regulator of the insulin pathway that modulates growth and proliferation.

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    08/29/03 | Crystal structure of Pyrococcus furiosus phosphoglucose isomerase. Implications for substrate binding and catalysis.
    Berrisford JM, Akerboom J, Turnbull AP, de Geus D, Sedelnikova SE, Staton I, McLeod CW, Verhees CH, van der Oost J, Rice DW, Baker PJ
    The Journal of Biological Chemistry. 2003 Aug 29;278(35):33290-7. doi: 10.1074/jbc.M305170200

    Phosphoglucose isomerase (PGI) catalyzes the reversible isomerization between d-fructose 6-phosphate and d-glucose 6-phosphate as part of the glycolytic pathway. PGI from the Archaea Pyrococcus furiosus (Pfu) was crystallized, and its structure was determined by x-ray diffraction to a 2-A resolution. Structural comparison of this archaeal PGI with the previously solved structures of bacterial and eukaryotic PGIs reveals a completely different structure. Each subunit of the homodimeric Pfu PGI consists of a cupin domain, for which the overall structure is similar to other cupin domain-containing proteins, and includes a conserved transition metal-binding site. Biochemical data on the recombinant enzyme suggests that Fe2+ is bound to Pfu PGI. However, as catalytic activity is not strongly influenced either by the replacement of Fe2+ by a range of transition metals or by the presence or absence of the bound metal ion, we suggest that the metal may not be directly involved in catalysis but rather may be implicated in substrate recognition.

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    08/08/03 | Diapause in the pea aphid (Acyrthosiphon pisum) is a slowing but not a cessation of development.
    Shingleton AW, Sisk GC, Stern DL
    BMC Dev Biol. 2003 Aug 8;3:7. doi: 10.1186/1471-213X-3-7

    BACKGROUND: Many insects undergo a period of arrested development, called diapause, to avoid seasonally recurring adverse conditions. Whilst the phenology and endocrinology of insect diapause have been well studied, there has been comparatively little research into the developmental details of diapause. We investigated developmental aspects of diapause in sexually-produced embryos of the pea aphid, Acyrthosiphon pisum.

    RESULTS: We found that early stages of embryogenesis progressed at a temperature-independent rate, characteristic of diapause, whereas later stages of embryogenesis progressed at a temperature-dependent rate. However, embryos maintained at very high temperatures during the temperature-independent stage showed severe developmental abnormalities. Under no temperature regime did embryos display a distinct resting stage. Rather, morphological development progressed slowly but continuously throughout embryogenesis.

    CONCLUSION: Diapause in the pea aphid, and perhaps in many other insects, is a temperature-independent slowing but not a cessation of morphological development. This suggests that the mechanisms limiting developmental rate during diapause may be the same as those controlling developmental rate at other stages of growth.

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    08/28/03 | Power-law for axon diameters at branch point.
    Chklovskii DB, Stepanyants A
    BMC Neuroscience. 2003 Aug 28;4:18. doi: 10.1016/j.tins.2005.05.006

    Axon calibers vary widely among different animals, neuron classes, and even within the same neuron. What determines the diameter of axon branches?

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    08/21/03 | Regulatory evolution of shavenbaby/ovo underlies multiple cases of morphological parallelism.
    Sucena E, Delon I, Jones I, Payre F, Stern DL
    Nature. 2003 Aug 21;424(6951):935-8. doi: 10.1038/nature01768

    Cases of convergent evolution that involve changes in the same developmental pathway, called parallelism, provide evidence that a limited number of developmental changes are available to evolve a particular phenotype. To our knowledge, in no case are the genetic changes underlying morphological convergence understood. However, morphological convergence is not generally assumed to imply developmental parallelism. Here we investigate a case of convergence of larval morphology in insects and show that the loss of particular trichomes, observed in one species of the Drosophila melanogaster species group, has independently evolved multiple times in the distantly related D. virilis species group. We present genetic and gene expression data showing that regulatory changes of the shavenbaby/ovo (svb/ovo) gene underlie all independent cases of this morphological convergence. Our results indicate that some developmental regulators might preferentially accumulate evolutionary changes and that morphological parallelism might therefore be more common than previously appreciated.

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