title: DACH1 regulates cell cycle progression of myeloid cells through the control of cyclin D, Cdk 4/6 and p21Cip1.
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.
authors.affiliation: School of Life Science and Biotechnology, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Jae-Woong
authors.initials: JW
authors.lastname: Lee
authors.forename: Hyeng-Soo
authors.initials: HS
authors.lastname: Kim
authors.forename: Seonggon
authors.initials: S
authors.lastname: Kim
authors.forename: Junmo
authors.initials: J
authors.lastname: Hwang
authors.forename: Young Hun
authors.initials: YH
authors.lastname: Kim
authors.forename: Ga Young
authors.initials: GY
authors.lastname: Lim
authors.forename: Wern-Joo
authors.initials: WJ
authors.lastname: Sohn
authors.forename: Suk-Ran
authors.initials: SR
authors.lastname: Yoon
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Tae Sung
authors.initials: TS
authors.lastname: Park
authors.forename: Kwon Moo
authors.initials: KM
authors.lastname: Park
authors.forename: Zae Young
authors.initials: ZY
authors.lastname: Ryoo
authors.forename: Sanggyu
authors.initials: S
authors.lastname: Lee
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002478:Cells, Cultured; D056741:Cyclin D / Q000378:metabolism*; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism*; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D005136:Eye Proteins / Q000235:genetics / Q000502:physiology*; D055785:Gene Knockdown Techniques; D018922:HL-60 Cells; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis; D051379:Mice; D022423:Myeloid Cells / Q000502:physiology*; D050814:Octamer Transcription Factor-3 / Q000096:biosynthesis; D055748:SOXB1 Transcription Factors / Q000096:biosynthesis; D013234:Stem Cells / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014161:Transduction, Genetic; D015854:Up-Regulation
chemical_list: C493956:CDKN1A protein, human; D056741:Cyclin D; D050759:Cyclin-Dependent Kinase Inhibitor p21; C486747:DACH1 protein, human; D005136:Eye Proteins; C000715467:KLF4 protein, human; C000715468:Klf4 protein, mouse; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors; C495900:CDK4 protein, human; C495911:CDK6 protein, human; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6