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Differentiation of Acute Promyelocytic Leukemia Cells by All-trans Retinoic Acid and A Cyclin-Dependent Kinase Inhibitor Involves Dissociation of a CDK4/C/EBP and#949; Complex| Abstract

Journal of Biochemistry and Cell Biology
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  • Research Article   
  • J Biochem Cell Biol 2018, Vol 1(1): 103

Differentiation of Acute Promyelocytic Leukemia Cells by All-trans Retinoic Acid and A Cyclin-Dependent Kinase Inhibitor Involves Dissociation of a CDK4/C/EBP ε Complex

Tsolkas G1, Komninou D2 and Papanikolaou NA3*
1Department of Bioengineering, Imperial College, , London, UK
2Advanced Technological Educational Institute (ATEI) of Thessaloniki, , Macedonia, Greece
3Laboratory of Biological Chemistry, Aristotle University of Thessaloniki School of Medicine, , Macedonia, Greece
*Corresponding Author : Papanikolaou NA, Laboratory of Biological Chemistry, Aristotle University of Thessaloniki School of Medicine, Macedonia, Greece, Tel: (+30)2310999003, Fax: (+30) 2310999004, Email: [email protected]

Received Date: Jan 23, 2018 / Accepted Date: Feb 13, 2018 / Published Date: Feb 23, 2018

Abstract

Cell differentiation involves exiting the cell cycle and activating gene programs that are responsible for differentiation. The cyclin-dependent CDK4 kinase regulates the cell cycle at the G1/S stage and is an important molecule that contributes to tumorigenic mechanisms in nearly all neoplasms. CDK4 links the cell cycle to mitogenic/anti-mitogenic signals with unknown mechanisms cooperating with Cyclin D1. The cellular "decision" for differentiation or continuous proliferation occurs predominantly in the G1/S phase with mechanisms dependent on the type of cells with CDK4 kinase having a key role. We have recently demonstrated that the combination of sub-pharmaceutical doses of retinoic acid (ATPA) and CDK1/CDK2 inhibitors in acute promyelocytic leukemia (APL) cells induces degradation of CDK4 protein by simultaneously differentiating cells into granulocytes. In this paper we report that in proliferating NB4 cells, C/EBPε and CDK4 interact whereas treatment of the cells with a CDK1/CDK2 inhibitor and sub-pharmacological levels of all-trans retinoic acid leads to dissociation of the two proteins concomitantly with granulocytic differentiation of the leukemic cells. Our data suggest that CDK4/C/EBPε complexes may contribute to APL cell proliferation and that their dissociation may be required for differentiation.

Keywords: Cell differentiation; Retinoblastoma; Granulocytes; Mitogenic/Anti-mitogenic signals.

Citation: Tsolkas G, Komninou D, Papanikolaou NA (2018) Differentiation of Acute Promyelocytic Leukemia Cells by All-trans Retinoic Acid and A Cyclin-Dependent Kinase Inhibitor Involves Dissociation of a CDK4/C/EBP ε Complex. J Biochem Cell Biol 1: 103.

Copyright: © 2018 Tsolkas G, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

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