TY - JOUR
T1 - PML-retinoic acid receptor α inhibits PML IV enhancement of PU.1-induced C/EBPε expression in myeloid differentiation
AU - Yoshida, Hitoshi
AU - Ichikawa, Hitoshi
AU - Tagata, Yusuke
AU - Katsumoto, Takuo
AU - Ohnishi, Kazunori
AU - Akao, Yukihiro
AU - Naoe, Tomoki
AU - Pandolfi, Pier Paolo
AU - Kitabayashi, Issay
PY - 2007/8
Y1 - 2007/8
N2 - 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.
AB - 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.
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U2 - 10.1128/MCB.02422-06
DO - 10.1128/MCB.02422-06
M3 - Article
C2 - 17562868
AN - SCOPUS:34547873122
SN - 0270-7306
VL - 27
SP - 5819
EP - 5834
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 16
ER -