DACH1 regulates cell cycle progression of myeloid cells through the control of cyclin D, Cdk 4/6 and p21^Cip1

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• 作者：Jae-Woong Lee^a ; Hyeng-Soo Kim^a ; Seonggon Kim^a ; Junmo Hwang^a ; Young Hun Kim^a ; Ga Young Lim^a ; Wern-Joo Sohn^b ; Suk-Ran Yoon^c ; Jae-Young Kim^b ; Tae Sung Park^d ; Kwon Moo Park^e ; Zae Young Ryoo^a ; Sanggyu Lee^a ; ^{slee@knu.ac.kr}
• 关键词：DACH1 ; Myeloid leukemia ; CCND ; p21Cip1 ; MLL-AF9
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：30 March, 2012
• 卷：420
• 期：1
• 页码：91-95
• 文件大小：404 K

摘要

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.