PU.1 directly regulates cdk6 gene expression, linking the cell proliferation and differentiation programs in erythroid cells.
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.
Choe
Kevin S
KS
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Ujhelly
Olga
O
Wontakal
Sandeep N
SN
Skoultchi
Arthur I
AI
D000818:Animals; D002453:Cell Cycle; D002454:Cell Differentiation; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051361:Cyclin-Dependent Kinase 6 / Q000378:metabolism*; D041905:Erythroid Cells / Q000166:cytology*; D050982:GATA1 Transcription Factor / Q000378:metabolism; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D051379:Mice; D008954:Models, Biological; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D000099232:Proto-Oncogene Protein Spi-1
D051361:Cyclin-Dependent Kinase 6; D050982:GATA1 Transcription Factor; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1; C494689:Gata1 protein, mouse; C495912:Cdk6 protein, mouse