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

Asiya Batool; Sabreena Aashaq; Khurshid Iqbal Andrabi

doi:10.1016/j.ejcb.2017.03.013

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

Eur J Cell Biol. 2017 Jun;96(4):325-336. doi: 10.1016/j.ejcb.2017.03.013. Epub 2017 Apr 8.

Authors

Asiya Batool¹, Sabreena Aashaq², Khurshid Iqbal Andrabi²

Affiliations

¹ Department of Biotechnology and Bioinformatics, University of Kashmir, Science Block, Ground Floor, Srinagar, Jammu and Kashmir 190006, India. Electronic address: asiyabatool16@gmail.com.
² Department of Biotechnology and Bioinformatics, University of Kashmir, Science Block, Ground Floor, Srinagar, Jammu and Kashmir 190006, India.

PMID: 28427795
DOI: 10.1016/j.ejcb.2017.03.013

Abstract

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.

Keywords: 4E-BP; Post-translational modification; Rapamycin; eIF4E; mTOR.

Publication types

Review

MeSH terms

Adaptor Proteins, Signal Transducing / genetics*
Adaptor Proteins, Signal Transducing / metabolism
Animals
Antibiotics, Antineoplastic / therapeutic use
Cell Cycle Proteins
Cell Transformation, Neoplastic / drug effects
Cell Transformation, Neoplastic / genetics
Cell Transformation, Neoplastic / metabolism
Cell Transformation, Neoplastic / pathology
Gene Expression Regulation, Neoplastic*
Humans
Mechanistic Target of Rapamycin Complex 1 / genetics*
Mechanistic Target of Rapamycin Complex 1 / metabolism
Neoplasms / drug therapy
Neoplasms / genetics*
Neoplasms / metabolism
Neoplasms / pathology
Phosphoproteins / genetics*
Phosphoproteins / metabolism
Phosphorylation / drug effects
Protein Biosynthesis
Protein Isoforms / genetics
Protein Isoforms / metabolism
Protein Processing, Post-Translational*
Signal Transduction
Sirolimus / therapeutic use
TOR Serine-Threonine Kinases / genetics*
TOR Serine-Threonine Kinases / metabolism

Substances

Adaptor Proteins, Signal Transducing
Antibiotics, Antineoplastic
Cell Cycle Proteins
EIF4EBP1 protein, human
Phosphoproteins
Protein Isoforms
MTOR protein, human
Mechanistic Target of Rapamycin Complex 1
TOR Serine-Threonine Kinases
Sirolimus