Investigation into the nuclear functions of ribosomal S6 kinases.
Doctoral thesis, UCL (University College London).
The S6 Kinases (S6Ks) have been linked to a number of cellular processes, including translation, insulin metabolism, cell survival and RNA splicing. Of the two S6 Kinase isoforms, the understanding of the roles and functions of S6K2 has been lacking in comparison to its S6K1 counterpart. S6K2, with the presence of a C-terminal NLS not found on S6K1 would indicate that S6K2 would have distinct nuclear functions. Here we present evidence that S6K2 is able to associate with a number of binding proteins in the cell nucleus, in particular with the heterogeneous ribonucleoproteins (hnRNPs). Both S6K2 and its upstream regulating kinase, mTOR interact with hnRNP F/H as part of a dynamic macromolecular complex in vivo. Association of mTOR, but not S6K2 with hnRNP F/H could be regulated by growth factors. The mTOR-hnRNP F/H interaction could also be blocked by inhibitors of upstream kinases essential for mTORC1 activation. In addition, we define a new role of hnRNP F in driving cell proliferation which could be partially attenuated by Rapamycin treatment. These results demonstrate that the mTOR and S6K2 association with hnRNPs has not just an interactive, but also a functional role.
|Title:||Investigation into the nuclear functions of ribosomal S6 kinases|
|Additional information:||Authorisation for digitisation not received|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of) > Structural and Molecular Biology|
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