1,758 research outputs found

    Universal flux-fluctuation law in small systems

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    We thank Dr. DeMenezes for providing the microchip data. This work was partially supported by the NSF of China under Grant Nos. 11135001, 11275003. Y.C.L. was supported by ARO under Grant No. W911NF-14-1-0504.Peer reviewedPublisher PD

    Optimization and resilience of complex supply-demand networks

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    Acknowledgments This work was supported by NSF under Grant No. 1441352. SPZ and ZGH were supported by NSF of China under Grants No. 11135001 and No. 11275003. ZGH thanks Prof Liang Huang and Xin-Jian Xu for helpful discussions.Peer reviewedPublisher PD

    A Novel Thyroid Hormone Receptor Isoform, TRβ2-46, Promotes SKP2 Expression and Retinoblastoma Cell Proliferation

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    Published under exclusive license by The American Society for Biochemistry and Molecular Biology, Inc. Retinoblastoma is a childhood retinal tumor that develops from cone photoreceptor precursors in response to inactivating RB1 mutations and loss of functional RB protein. The cone precursor\u27s response to RB loss involves cell type–specific signaling circuitry that helps to drive tumorigenesis. One component of the cone precursor circuitry, the thyroid hormone receptor β2 (TRβ2), enables the aberrant proliferation of diverse RB-deficient cells in part by opposing the down-regulation of S-phase kinase-associated protein 2 (SKP2) by the more widely expressed and tumor-suppressive TRβ1. However, it is unclear how TRβ2 opposes TRβ1 to enable SKP2 expression and cell proliferation. Here, we show that in human retinoblastoma cells TRβ2 mRNA encodes two TRβ2 protein isoforms: a predominantly cytoplasmic 54-kDa protein (TRβ2-54) corresponding to the well-characterized full-length murine Trβ2 and an N-terminally truncated and exclusively cytoplasmic 46-kDa protein (TRβ2-46) that starts at Met-79. Whereas TRβ2 knockdown decreased SKP2 expression and impaired retinoblastoma cell cycle progression, re-expression of TRβ2-46 but not TRβ2-54 stabilized SKP2 and restored proliferation to an extent similar to that of ectopic SKP2 restoration. We conclude that TRβ2-46 is an oncogenic thyroid hormone receptor isoform that promotes SKP2 expression and SKP2-dependent retinoblastoma cell proliferation
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