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

Kevin S. Choe, Olga Ujhelly, Sandeep N. Wontakal, Arthur I. Skoultchi

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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 G1 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 G1 phase of the cell cycle, the period during which the decision to differentiate is made.

Original languageEnglish (US)
Pages (from-to)3044-3052
Number of pages9
JournalJournal of Biological Chemistry
Volume285
Issue number5
DOIs
StatePublished - Jan 29 2010

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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