Transcriptional and ERK1/2-dependent synergistic upregulation of p21cip1/waf1 associated with steel factor synergy in MO7e

Y. Lee, C. Mantel, N. Anzai, S. E. Braun, Hal Broxmeyer

Research output: Contribution to journalArticle

18 Citations (Scopus)

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

Fingerprint

Stem Cell Factor
Granulocyte-Macrophage Colony-Stimulating Factor
Up-Regulation
Cyclin-Dependent Kinase Inhibitor Proteins
Cells
Mitogen-Activated Protein Kinase 3
Cyclin-Dependent Kinases
MAP Kinase Signaling System
Mitogen-Activated Protein Kinase 1
p38 Mitogen-Activated Protein Kinases
Ribonucleases
Assays
Cell Cycle
Chemical activation
Cell Line
Messenger RNA
Proteins

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Transcriptional and ERK1/2-dependent synergistic upregulation of p21cip1/waf1 associated with steel factor synergy in MO7e. / Lee, Y.; Mantel, C.; Anzai, N.; Braun, S. E.; Broxmeyer, Hal.

In: Biochemical and Biophysical Research Communications, Vol. 280, No. 3, 2001, p. 675-683.

Research output: Contribution to journalArticle

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AU - Braun, S. E.

AU - Broxmeyer, Hal

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