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Biochem Biophys Res Commun. 2008 Jan 11;365(2):258-65. Epub 2007 Nov 6.

Coiled-coil domain of PML is essential for the aberrant dynamics of PML-RARalpha, resulting in sequestration and decreased mobility of SMRT.

Author information

1
Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiaotong University School of Medicine (SJTU-SM), No. 280, Chong-Qing South Road, Shanghai 200025, China.

Abstract

Promyelocytic leukemia-retinoic acid receptor alpha (PML-RARalpha) is the most frequent RARalpha fusion protein in acute promyelocytic leukemia (APL). Our previous study has demonstrated that, compared with RARalpha, PML-RARalpha had reduced intranuclear mobility accompanied with mislocalization. To understand the molecular basis for the altered dynamics of PML-RARalpha fusion protein, we performed FRAP analysis at a single cell level. Results indicated that three known sumoylation site mutated PML-RARalpha had same intracellular localization and reduced mobility as wild-type counterpart. The coiled-coil domain of PML is responsible for the aberrant dynamics of PML-RARalpha. In addition, we revealed that co-repressor SMRT co-localized with PML-RARalpha, resulting in the immobilization of SMRT while ATRA treatment eliminated their association and reversed the immobile effect of SMRT. Furthermore, co-activator CBP, co-localized with PML-RARalpha in an ATRA-independent way, was demonstrated as a high dynamic intranuclear molecule. These results would shed new insights for the molecular mechanisms of PML-RARalpha-associated leukemogenesis.

PMID:
17991421
DOI:
10.1016/j.bbrc.2007.10.184
[Indexed for MEDLINE]

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