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  1. Article ; Online: GEF-independent Ran activation shifts a fraction of the protein to the cytoplasm and promotes cell proliferation

    Jinhan Zhou / Yuping Tan / Yuqing Zhang / Aiping Tong / Xiaofei Shen / Xiaodong Sun / Da Jia / Qingxiang Sun

    Molecular Biomedicine, Vol 1, Iss 1, Pp 1-

    2020  Volume 13

    Abstract: Abstract Ran (Ras-related nuclear protein) plays several important roles in nucleo-cytoplasmic transport, mitotic spindle formation, nuclear envelope/nuclear pore complex assembly, and other functions in the cytoplasm, as well as in cellular ... ...

    Abstract Abstract Ran (Ras-related nuclear protein) plays several important roles in nucleo-cytoplasmic transport, mitotic spindle formation, nuclear envelope/nuclear pore complex assembly, and other functions in the cytoplasm, as well as in cellular transformation when switched on. Unlike other members of the GTPase superfamily, Ran binds more tightly to GDP than to GTP due to the presence of an auto-inhibitory C-terminal tail. Multiple missense mutations in the C-terminus of Ran occur in cancers, but their biological significance remains unclear. Here, the quantitative GDP/GTP binding preference of four engineered mutations with unstable C-termini was analyzed using a devised mant-GDP dissociation assay. The results showed that the impact of different C-terminal mutations depends on multiple factors. Although these mutants were more GTP-loaded in human cells, they were shown to be more cytoplasmic, and to support nuclear transport with minimally or partially reduced efficiency. Further, several Ran cancer mutants were compromised in autoinhibition, slightly more GTP-bound, more cytoplasmic, and enhanced the proliferation of A549 and HeLa cells in vitro. Thus, our work reveals a new route of Ran activation independent of guanine nucleotide exchange factor (GEF), which may account for the hyper-proliferation induced by Ran cancer mutations.
    Keywords Small GTPases ; Nuclear transport ; GTP bias ; Activation ; Cancer mutations ; Medicine ; R
    Subject code 570
    Language English
    Publishing date 2020-12-01T00:00:00Z
    Publisher Springer
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Distinct RanBP1 nuclear export and cargo dissociation mechanisms between fungi and animals

    Yuling Li / Jinhan Zhou / Sui Min / Yang Zhang / Yuqing Zhang / Qiao Zhou / Xiaofei Shen / Da Jia / Junhong Han / Qingxiang Sun

    eLife, Vol

    2019  Volume 8

    Abstract: Ran binding protein 1 (RanBP1) is a cytoplasmic-enriched and nuclear-cytoplasmic shuttling protein, playing important roles in nuclear transport. Much of what we know about RanBP1 is learned from fungi. Intrigued by the long-standing paradox of harboring ...

    Abstract Ran binding protein 1 (RanBP1) is a cytoplasmic-enriched and nuclear-cytoplasmic shuttling protein, playing important roles in nuclear transport. Much of what we know about RanBP1 is learned from fungi. Intrigued by the long-standing paradox of harboring an extra NES in animal RanBP1, we discovered utterly unexpected cargo dissociation and nuclear export mechanisms for animal RanBP1. In contrast to CRM1-RanGTP sequestration mechanism of cargo dissociation in fungi, animal RanBP1 solely sequestered RanGTP from nuclear export complexes. In fungi, RanBP1, CRM1 and RanGTP formed a 1:1:1 nuclear export complex; in contrast, animal RanBP1, CRM1 and RanGTP formed a 1:1:2 nuclear export complex. The key feature for the two mechanistic changes from fungi to animals was the loss of affinity between RanBP1-RanGTP and CRM1, since residues mediating their interaction in fungi were not conserved in animals. The biological significances of these different mechanisms in fungi and animals were also studied.
    Keywords nuclear transport ; RanBP1 ; nuclear export signal ; fungi ; animal ; distinct mechanism ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
    Subject code 630
    Language English
    Publishing date 2019-04-01T00:00:00Z
    Publisher eLife Sciences Publications Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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