DEPTOR in Skeletal Development and Diseases.

Jose Miguel Perez-Tejeiro,Fabiana Csukasi

doi:10.3389/fgene.2021.667283

Abstract

Discovered in 2009, the DEP-domain containing mTOR-interacting protein, DEPTOR, is a known regulator of the mechanistic target of rapamycin (mTOR), an evolutionarily conserved kinase that regulates diverse cellular processes in response to environmental stimuli. DEPTOR was originally identified as a negative regulator of mTOR complexes 1 (mTORC1) and 2 (mTORC2). However, recent discoveries have started to unravel the roles of DEPTOR in mTOR-independent responses. In the past few years, mTOR emerged as an important regulator of skeletal development, growth, and homeostasis; the dysregulation of its activity contributes to the development of several skeletal diseases, both chronic and genetic. Even more recently, several groups have reported on the relevance of DEPTOR in skeletal biology through its action on mTOR-dependent and mTOR-independent pathways. In this review, we summarize the current understanding of DEPTOR in skeletal development and disease.

Highlights

Discovered in 2009, the DEP-domain containing mTOR-interacting protein, DEPTOR, is a known regulator of the mechanistic target of rapamycin, an evolutionarily conserved kinase that regulates diverse cellular processes in response to environmental stimuli
In the past few years, mTOR emerged as an important regulator of skeletal development, growth, and homeostasis; the dysregulation of its activity contributes to the development of several skeletal diseases, both chronic and genetic
Studies discovered its function as a member of the mechanistic target of rapamycin complexes, mTOR complexes 1 (mTORC1), and mTOR complex 2 (mTORC2) (Peterson et al, 2009)

Summary

Introduction

Discovered in 2009, the DEP-domain containing mTOR-interacting protein, DEPTOR, is a known regulator of the mechanistic target of rapamycin (mTOR), an evolutionarily conserved kinase that regulates diverse cellular processes in response to environmental stimuli. Hormones play a role in the regulation of DEPTOR gene expression; androgen and estrogen receptors have been suggested as negative and positive regulators of DEPTOR, respectively (Kanno et al, 2015; Parvani et al, 2015) Glucocorticoids such as dexamethasone and corticosterone have been associated with the transcriptional control of DEPTOR, positively regulating its expression (Laplante et al, 2012). Two transcriptional regulators, Six and Baf60c, coordinately stimulate Deptor expression in muscle cells (Meng et al, 2013)

Objectives

Conclusion