PML-retinoic acid receptor α inhibits PML IV enhancement of PU.1-induced C/EBPε expression in myeloid differentiation

Hitoshi Yoshida, Hitoshi Ichikawa, Yusuke Tagata, Takuo Katsumoto, Kazunori Ohnishi, Yukihiro Akao, Tomoki Naoe, Pier Paolo Pandolfi, Issay Kitabayashi

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

Abstract

PML and PU.1 play important roles in myeloid differentiation. PML-deficient mice have an impaired capacity for terminal maturation of their myeloid precursor cells. This finding has been explained, at least in part, by the lack of PML action to modulate retinoic acid-differentiating activities. In this study, we found that C/EBPε expression is reduced in PML-deflcient mice. We showed that PU.1 directly activates the transcription of the C/EBPε gene that is essential for granulocytic differentiation. The type IV isoform of PML interacted with PU.1, promoted its association with p300, and then enhanced PU.1-induced transcription and granulocytic differentiation. In contrast to PML IV, the leukemia-associated PML-retinoic acid receptor α fusion protein dissociated the PU.1/PML IV/p300 complex and inhibited PU.1-induced transcription. These results suggest a novel pathogenic mechanism of the PML-retinoic acid receptor α fusion protein in acute promyelocyte leukemia.

Original languageEnglish
Pages (from-to)5819-5834
Number of pages16
JournalMolecular and Cellular Biology
Volume27
Issue number16
DOIs
Publication statusPublished - 08-2007
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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