Specificity of PML and PML-RARα SUMO modification in recruiting Daxx
Date Issued
2008
Date
2008
Author(s)
Huang, Nai-Jia
Abstract
PML (promyelocytic leukemia gene) fused to retinoic acid receptor α (RARα),erived from the t(15;17) translocation, causes acute promyelocytic leukemia (APL).everal transcriptional corepressors such as NcoR, SMRT and HDACs were shown tossociate with PML-RARα, leading to transcriptional repression. Besides, recent reportsndicated that Daxx could contribute to transcriptional repression ofML/RARα-targeted genes via interacting with SUMO modification at Lys160 of PMLortion. The specificity of how Daxx binds to sumoylated PML has not been wellharacterized. In this study, we used different approaches to show that all threeUMO-acceptor Lys sites of PML and PML-RARα are important for Daxx interaction.n addition, we found that sumoylation level of PML at each Lys acceptor site isffected by each other when individual sumoylation site was mutated, indicating thatML sumoylation at each Lys acceptor is not independent. In addition, we foundxogenous Daxx SUMO-interacting motif (SIM) peptide could reverse Daxx-elicitedepression on PML-RARα-mediated reporter activity and could affect APL celline-NB4 cells proliferation rate. Together, our studies elucidate theumoylation-mediated interaction between PML or PML-RARα and Daxx and providehe evidence that Daxx-SIM peptide may be considered a potential agent for blockingPL-mediated transformation phenotype.
Subjects
promyelocytic leukemia (PML)
retinoic acid receptor α (RARα)
Fas death domain associated protein (Daxx)
acute promyelocytic leukemia (APL)
small ubiquitin-related
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