Young, LC;
(2016)
Regulation of the RAS-ERK pathway by SHOC2.
Doctoral thesis , UCL (University College London).
Abstract
SHOC2 is mutated in Noonan syndrome and plays a key role in the activation of the RAS-ERK pathway, which is upregulated in the majority of human cancers. SHOC2 functions as a PP1 regulatory protein and as an effector of MRAS. SHOC2 and MRAS form a complex with SCRIB, a polarity protein with tumour suppressor properties. SCRIB functions as a PP1 regulatory protein and a model is proposed whereby SCRIB inhibits the ERK pathway by antagonising SHOC2 complex-mediated RAF dephosphorylation through a mechanism which is dependent on the SCRIB-PP1 interaction. SHOC2 complex function is required for EGF-stimulated RAF dimerisation and is selectively required for the malignant properties of tumour cells with mutant RAS. MRAS and SHOC2 also play a key role in polarised migration and I propose that MRAS, through its ability to recruit a complex with paradoxical components, coordinates ERK pathway dynamics with polarity. The SHOC2-MRAS-PP1 complex plays a key role during tumourigenic growth and is an attractive target for pharmacological inhibition in malignancies with upregulated RAS-ERK pathway activity.
| Type: | Thesis (Doctoral) |
|---|---|
| Title: | Regulation of the RAS-ERK pathway by SHOC2 |
| Event: | UCL |
| Language: | English |
| Keywords: | SHOC2, MRAS, SCRIB, PP1, migration, cancer, RAS, RAF, polarity |
| UCL classification: | UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1502242 |
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