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
Received Date: Jan 23, 2018 / Accepted Date: Feb 13, 2018 / Published Date: Feb 23, 2018
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
Select your language of interest to view the total content in your interested language
Share This Article
Open Access Journals
- Total views: 2080
- [From(publication date): 0-2018 - Jan 29, 2022]
- Breakdown by view type
- HTML page views: 1739
- PDF downloads: 341