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

• Published in: Biochemical and biophysical research communications Vol. 420; no. 1; pp. 91 - 95
• Main Authors: Lee, Jae-Woong, Kim, Hyeng-Soo, Kim, Seonggon, Hwang, Junmo, Kim, Young Hun, Lim, Ga Young, Sohn, Wern-Joo, Yoon, Suk-Ran, Kim, Jae-Young, Park, Tae Sung, Park, Kwon Moo, Ryoo, Zae Young, Lee, Sanggyu
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 30.03.2012
• Subjects: Animals; CCND; Cell Cycle; Cells, Cultured; Cyclin D - metabolism; Cyclin-Dependent Kinase 4 - metabolism; Cyclin-Dependent Kinase 6 - metabolism; Cyclin-Dependent Kinase Inhibitor p21 - metabolism; DACH1; Eye Proteins - genetics; Eye Proteins - physiology; Gene Knockdown Techniques; HL-60 Cells; Humans; Kruppel-Like Transcription Factors - biosynthesis; Mice; MLL-AF9; Myeloid Cells - physiology; Myeloid leukemia; Octamer Transcription Factor-3 - biosynthesis; p21Cip1; SOXB1 Transcription Factors - biosynthesis; Stem Cells - physiology; Transcription Factors - genetics; Transcription Factors - physiology; Transduction, Genetic; Up-Regulation; MLL-AF9; p21Cip1; CCND; DACH1; Myeloid leukemia
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2012.02.120

► DACH1 increases cyclin D, F and Cdk 1, 4, 6 in mouse myeloid progenitor cells. ► The knockdown of DACH1 blocked the cell cycle progression of HL-60 cells. ► The novel effect of DACH1 related with cell cycle regulation and leukemogenesis. 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 p27Kip1 and repressed p21Cip1, 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 p21Cip1, 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.