Deregulated expression of the PU.1 transcription factor blocks murine erythroleukemia cell terminal differentiation

Govinda Rao, Natasha Rekhtman, Genhong Cheng, Tatiana Krasikov, Arthur I. Skoultchi

Research output: Contribution to journalArticle

85 Citations (Scopus)

Abstract

Murine erythroleukemia (MEL) cells are transformed erythroid precursors that are blocked from completing the Late stages of erythroid differentiation. A frequent event in the generation of these malignant cells is deregulation of the hematopoietic-specific transcription factor PU.1 (Spi-1) by retroviral insertion of the spleen-focus-forming virus component of Friend virus. During chemically induced reinitiation of MEL cell terminal differentiation, expression of PU.1 is rapidly down-regulated, suggesting that PU.1 might interfere with processes required for terminal differentiation of erythroid precursors. To investigate the role of PU.1 in erythroid differentiation we transfected MEL cells with a PU.1 cDNA controlled by the eucaryotic translation elongation factor EF1α promoter. Deregulated expression of PU.1 blocked chemically induced differentiation and terminal cell division. Deregulated expression of two other protooncogenes, c-myc and c-myb, also has been shown to block MEL differentiation. We present evidence that PU.1 inhibits terminal differentiation at an earlier step than c-Myc and c-Myb, Thus reinitiation of MEL cell terminal differentiation appears to be controlled by an ordered program of turning off several protooncogenes. Down-regulation of PU.1 may be a very early step in this program.

Original languageEnglish (US)
Pages (from-to)123-131
Number of pages9
JournalOncogene
Volume14
Issue number1
StatePublished - 1997

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Leukemia, Erythroblastic, Acute
Cell Differentiation
Transcription Factors
Spleen Focus-Forming Viruses
Friend murine leukemia virus
Peptide Elongation Factors
Viral Structures
Erythroid Precursor Cells
Cell Division
Down-Regulation
Complementary DNA

Keywords

  • c-myb
  • c-myc
  • Differentiation
  • MEL cells
  • PU.1
  • Spi-1

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Deregulated expression of the PU.1 transcription factor blocks murine erythroleukemia cell terminal differentiation. / Rao, Govinda; Rekhtman, Natasha; Cheng, Genhong; Krasikov, Tatiana; Skoultchi, Arthur I.

In: Oncogene, Vol. 14, No. 1, 1997, p. 123-131.

Research output: Contribution to journalArticle

Rao, Govinda ; Rekhtman, Natasha ; Cheng, Genhong ; Krasikov, Tatiana ; Skoultchi, Arthur I. / Deregulated expression of the PU.1 transcription factor blocks murine erythroleukemia cell terminal differentiation. In: Oncogene. 1997 ; Vol. 14, No. 1. pp. 123-131.
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