4.5 Review

Reappraisal to the study of 4E-BP1 as an mTOR substrate - A normative critique

Journal

EUROPEAN JOURNAL OF CELL BIOLOGY
Volume 96, Issue 4, Pages 325-336

Publisher

ELSEVIER GMBH
DOI: 10.1016/j.ejcb.2017.03.013

Keywords

mTOR; 4E-BP; eIF4E; Rapamycin; Post-translational modification

Categories

Funding

  1. DST, India
  2. UGC, India
  3. Department of Science and Technology [140150/2014]
  4. University Grants Commission [23-12/2012]

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mTOR-4E-BP1 axis is regarded as the best oncogenic circuitry impinging on translational control whereby mTORC1 dictates post-translational regulation of 4E-BP1. This review provides new insights into the molecular network of signalling pathways highlighting the recent explosion of studies in respect to the deviant behaviour of 4E-BP1 towards mTORC1. Despite the striking conservation of mTOR nexus, the eccentric phosphorylation dynamics of 4E-BP1 negate the apparent linear architecture of mTORC1 attesting the importance of other kinases that may evoke cross-talks with the conventional frame, most of which are enlisted in the manuscript. We also throw light on the tenuous role of rapamycin in 4E-BP1 regulation, which further necessitates the evaluation of 4E-BP1 to envisage the underlying molecular mechanisms in the discovery of novel drugs of 4E-BP1 for new treatment strategies. Finally, the review brings forward comprehensive studies delineating the redundancy of 4E-BP isoforms in regulating translational control. (C) 2017 Elsevier GmbH. All rights reserved.

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