Coiled-coil domain of PML is essential for the aberrant dynamics of PML-RARalpha, resulting in sequestration and decreased mobility of SMRT.
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.[1]References
- Coiled-coil domain of PML is essential for the aberrant dynamics of PML-RARalpha, resulting in sequestration and decreased mobility of SMRT. Huang, Y., Qiu, J., Chen, G., Dong, S. Biochem. Biophys. Res. Commun. (2008) [Pubmed]
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