Transcriptional and ERK1/2-dependent synergistic upregulation of p21cip1/waf1associated with steel factor synergy in MO7e

Younghee Lee, Charlie Mantel, Naoyuki Anzai, Stephen E. Braun, Hal E. Broxmeyer

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Steel factor (SLF) plus GM-CSF induces proliferative synergy in myeloid progenitors and factor-dependent cell line MO7e. We previously reported that the protein level of cyclin-dependent kinase inhibitor p21cip1/waf1 (p21) increased synergistically when MO7e cells were stimulated with SLF plus GM-CSF and that p21 induction was required for SLF synergistic responses. Here we show that this p21 induction is regulated at the transcriptional level. Based on use of a multiprobe RNase protection assay, the synergistic increase of p21 mRNA was unique among many cell cycle regulators. While STAT5A and 5B were activated after stimulation with GM-CSF alone or SLF plus GM-CSF, there was no difference in activation between the groups, p44/42 MAP kinase (ERK1/2) was synergistically activated by SLF plus GM-CSF, but SAPK/JNK and p38 MAP kinase were not. Synergistic induction of p21 was significantly decreased with a MEK1 inhibitor, suggesting that the ERK1/2 pathway is involved in the synergistic increase of p21 after GM-CSF plus SLF stimulation.

Original languageEnglish (US)
Pages (from-to)675-683
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume280
Issue number3
DOIs
StatePublished - Jan 26 2001

Keywords

  • GM-CSF
  • MAP kinase
  • P21
  • Steel factor
  • Synergy
  • Transcriptional regulation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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