The role of mTOR-mediated signals during haemopoiesis and lineage commitment

Malik, N., Sansom, O. J. and Michie, A. M. (2018) The role of mTOR-mediated signals during haemopoiesis and lineage commitment. Biochemical Society Transactions, 46(5), pp. 1313-1324. (doi:10.1042/BST20180141) (PMID:30154096) (PMCID:PMC6195642)

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Abstract

The serine/threonine protein kinase mechanistic target of rapamycin (mTOR) has been implicated in the regulation of an array of cellular functions including protein and lipid synthesis, proliferation, cell size and survival. Here, we describe the role of mTOR during haemopoiesis within the context of mTORC1 and mTORC2, the distinct complexes in which it functions. The use of conditional transgenic mouse models specifically targeting individual mTOR signalling components, together with selective inhibitors, have generated a significant body of research emphasising the critical roles played by mTOR, and individual mTOR complexes, in haemopoietic lineage commitment and development. This review will describe the profound role of mTOR in embryogenesis and haemopoiesis, underscoring the importance of mTORC1 at the early stages of haemopoietic cell development, through modulation of stem cell potentiation and self-renewal, and erythroid and B cell lineage commitment. Furthermore, the relatively discrete role of mTORC2 in haemopoiesis will be explored during T cell development and B cell maturation. Collectively, this review aims to highlight the functional diversity of mTOR signalling and underline the importance of this pathway in haemopoiesis.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Malik, Natasha and Michie, Dr Alison and Sansom, Professor Owen
Authors: Malik, N., Sansom, O. J., and Michie, A. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Biochemical Society Transactions
Publisher:Portland Press
ISSN:0300-5127
ISSN (Online):1470-8752
Published Online:28 August 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Biochemical Society Transactions 46(5): 1313-1324
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
698661Elucidating the role of individual mTor complexes in the development and progression of chronic lymphocytic leukaemiaAlison MichieBloodwise (BLOODWIS)15041ICS - PAUL O'GORMAN LEUKAEMIA RESEARCH C