Review
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Dec 26, 2020; 12(12): 1553-1575
Published online Dec 26, 2020. doi: 10.4252/wjsc.v12.i12.1553
Minibrain-related kinase/dual-specificity tyrosine-regulated kinase 1B implication in stem/cancer stem cells biology
Nikolaos Kokkorakis, Maria Gaitanou
Nikolaos Kokkorakis, Maria Gaitanou, Laboratory of Cellular and Molecular Neurobiology-Stem Cells, Hellenic Pasteur Institute, Athens 11521, Greece
Author contributions: Kokkorakis Ν and Gaitanou M wrote the manuscript; All authors reviewed, edited and approved the final manuscript.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Maria Gaitanou, BSc, PhD, Research Assistant Professor, Laboratory of Cellular and Molecular Neurobiology-Stem Cells, Hellenic Pasteur Institute, Vas. Sofias 127, Athens 11521, Greece. mgaitanou@pasteur.gr
Received: July 10, 2020
Peer-review started: July 10, 2020
First decision: September 17, 2020
Revised: September 29, 2020
Accepted: October 15, 2020
Article in press: October 15, 2020
Published online: December 26, 2020
Abstract

Dual-specificity tyrosine phosphorylation-regulated kinase 1B (DYRK1B), also known as minibrain-related kinase (MIRK) is one of the best functionally studied members of the DYRK kinase family. DYRKs comprise a family of protein kinases that are emerging modulators of signal transduction pathways, cell proliferation and differentiation, survival, and cell motility. DYRKs were found to participate in several signaling pathways critical for development and cell homeostasis. In this review, we focus on the DYRK1B protein kinase from a functional point of view concerning the signaling pathways through which DYRK1B exerts its cell type-dependent function in a positive or negative manner, in development and human diseases. In particular, we focus on the physiological role of DYRK1B in behavior of stem cells in myogenesis, adipogenesis, spermatogenesis and neurogenesis, as well as in its pathological implication in cancer and metabolic syndrome. Thus, understanding of the molecular mechanisms that regulate signaling pathways is of high importance. Recent studies have identified a close regulatory connection between DYRK1B and the hedgehog (HH) signaling pathway. Here, we aim to bring together what is known about the functional integration and cross-talk between DYRK1B and several signaling pathways, such as HH, RAS and PI3K/mTOR/AKT, as well as how this might affect cellular and molecular processes in development, physiology, and pathology. Thus, this review summarizes the major known functions of DYRK1B kinase, as well as the mechanisms by which DYRK1B exerts its functions in development and human diseases focusing on the homeostasis of stem and cancer stem cells.

Keywords: Dual-specificity tyrosine-regulated kinase 1B, Minibrain-related kinase, Stem cells, Cancer stem cells, Quiescence, Cell proliferation/differentiation, Cell survival, Cancer, Hedgehog

Core Tip: Dual-specificity tyrosine phosphorylation-regulated kinase 1B (DYRK1B), also known as minibrain-related kinase (MIRK) is the well-studied member of the DYRK kinase family. DYRK1B is a key regulator of signaling pathways that control proliferation and differentiation, and is critical for developmental processes and cell homeostasis. In this review, we aim to bring together what is known about the functional integration and cross-talk between DYRK1B and several pathways, such as sonic hedgehog, RAS and PI3K/mTOR/AKT pathways and how this might affect the behavior of stem cells in development and disease, taking into consideration potent therapeutic interventions and approaches.