DACH1 regulates cell cycle progression of myeloid cells through the control of cyclin D, Cdk 4/6 and p21Cip1

Biochem Biophys Res Commun. 2012 Mar 30;420(1):91-5. doi: 10.1016/j.bbrc.2012.02.120. Epub 2012 Mar 3.

Abstract

The cell-fate determination factor Dachshund, a component of the Retinal Determination Gene Network (RDGN), has a role in breast tumor proliferation through the repression of cyclin D1 and several key regulators of embryonic stem cell function, such as Nanog and Sox2. However, little is known about the role of DACH1 in a myeloid lineage as a cell cycle regulator. Here, we identified the differential expression levels of extensive cell cycle regulators controlled by DACH1 in myeloid progenitor cells. The forced expression of DACH1 induced p27(Kip1) and repressed p21(Cip1), which is a pivotal characteristic of the myeloid progenitor. Furthermore, DACH1 significantly increased the expression of cyclin D1, D3, F, and Cdk 1, 4, and 6 in myeloid progenitor cells. The knockdown of DACH1 blocked the cell cycle progression of HL-60 promyeloblastic cells through the decrease of cyclin D1, D3, F, and Cdk 1, 4, and 6 and increase in p21(Cip1), which in turn decreased the phosphorylation of the Rb protein. The expression of Sox2, Oct4, and Klf4 was significantly up-regulated by the forced expression of DACH1 in mouse myeloid progenitor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle*
  • Cells, Cultured
  • Cyclin D / metabolism*
  • Cyclin-Dependent Kinase 4 / metabolism*
  • Cyclin-Dependent Kinase 6 / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • Eye Proteins / genetics
  • Eye Proteins / physiology*
  • Gene Knockdown Techniques
  • HL-60 Cells
  • Humans
  • Kruppel-Like Transcription Factors / biosynthesis
  • Mice
  • Myeloid Cells / physiology*
  • Octamer Transcription Factor-3 / biosynthesis
  • SOXB1 Transcription Factors / biosynthesis
  • Stem Cells / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transduction, Genetic
  • Up-Regulation

Substances

  • CDKN1A protein, human
  • Cyclin D
  • Cyclin-Dependent Kinase Inhibitor p21
  • DACH1 protein, human
  • Eye Proteins
  • GKLF protein
  • Kruppel-Like Transcription Factors
  • Octamer Transcription Factor-3
  • POU5F1 protein, human
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • Transcription Factors
  • CDK4 protein, human
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6