Regulation of megakaryocytic differentiation of K562 cells by FosB, a member of the Fos family of AP-1 transcription factors

J. K. Limb, S. Yoon, K. E. Lee, B. H. Kim, S. Lee, Y. S. Bae, G. J. Jhon, J. Kim

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

The regulation of megakaryocytic differentiation is poorly understood. Using K562 cells, which can partly recapitulate the process in response to phorbol 12-myristate 13-acetate (PMA), we performed microarray-based gene expression profiling to identify genes that play significant roles in megakaryopoiesis. Here, we describe the function of FosB, an AP-1 transcription factor. FosB is induced in PMA treated K562 cells in a sustained manner and forms an active AP-1 protein-DNA complex. Down-regulation of FosB with specific shRNAs inhibited the induction of CD41, a specific cell surface marker of megakaryocytes. We also show that activation of the PKC-MEK-ERK signaling pathway is required for induction of FosB and CD41. Finally,we cross-examined the microarray data in conjunction with gene function annotation data to identify additional target genes of FosB. We define 3 genes, INHBA, CD9, and ITGA2B as regulatory targets of FosB and show that CD9, in particular, is a direct target of FosB.

Original languageEnglish
Pages (from-to)1962-1973
Number of pages12
JournalCellular and Molecular Life Sciences
Volume66
Issue number11-12
DOIs
StatePublished - Jun 2009

Keywords

  • AP-1
  • CD41
  • FosB
  • K562
  • Megakaryocyte

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