PU.1 directly regulates cdk6 gene expression, linking the cell proliferation and differentiation programs in erythroid cells.

Abstract	Cell proliferation and differentiation are highly coordinated processes during normal development. Most leukemia cells are blocked from undergoing terminal differentiation and also exhibit uncontrolled proliferation. Dysregulated expression of transcription factor PU.1 is strongly associated with Friend virus-induced erythroleukemia. PU.1 inhibits erythroid differentiation by binding to and inhibiting GATA-1. PU.1 also may be involved in controlling proliferation of erythroid cells. We reported previously that the G(1) phase-specific cyclin-dependent kinase 6 (CDK6) also blocks erythroid differentiation. We now report that PU.1 directly stimulates transcription of the cdk6 gene in both normal erythroid progenitors and erythroleukemia cells, as well as in macrophages. We propose that PU.1 coordinates proliferation and differentiation in immature erythroid cells by inhibiting the GATA-1-mediated gene expression program and also by regulating expression of genes that control progression through the G(1) phase of the cell cycle, the period during which the decision to differentiate is made.
Authors	Kevin S Choe, Olga Ujhelly, Sandeep N Wontakal, Arthur I Skoultchi
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 285 Issue 5 Pg. 3044-52 (Jan 29 2010) ISSN: 1083-351X [Electronic] United States
PMID	19955566 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References	GATA1 Transcription Factor Gata1 protein, mouse Proto-Oncogene Proteins RNA, Small Interfering Trans-Activators proto-oncogene protein Spi-1 Cdk6 protein, mouse Cyclin-Dependent Kinase 6
Topics	Animals Cell Cycle Cell Differentiation Cell Line Cell Line, Tumor Cell Proliferation Cyclin-Dependent Kinase 6 (metabolism) Erythroid Cells (cytology) GATA1 Transcription Factor (metabolism) Gene Expression Regulation Gene Expression Regulation, Neoplastic Mice Models, Biological Proto-Oncogene Proteins (metabolism) RNA, Small Interfering (metabolism) Trans-Activators (metabolism)

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