Abstract
Promyelocytic leukemia zinc finger (PLZF) protein is a sequence-specific DNA-binding protein that represses the transcriptional activity of target genes such as those for cyclin A and the interleukin-3 receptor alpha chain. The PLZF gene becomes fused to the retinoic acid receptor alpha gene as a result of the t(11, 17)(q23;q21) chromosomal translocation that is associated with acute promyelocytic leukemia. We now show that endogenous PLZF in human promyelocytic leukemia HL-60 cells is modified by conjugation with SUMO-1 (small ubiquitin-related modifier-1) and that PLZF colocalizes with SUMO-1 in the nucleus of transfected human embryonic kidney 293T cells. Site-directed mutagenesis identified lysine 242 in the RD2 domain of human PLZF as the sumoylation site. A luciferase reporter gene assay suggested that SUMO-1 modification of this residue is required for transcriptional repression by PLZF, and an electrophoretic mobility shift assay showed that this modification increases the DNA binding activity of PLZF. PLZF-mediated regulation of the cell cycle and transcriptional repression of the cyclin A2 gene were also dependent on sumoylation of PLZF on lysine 242. These results demonstrate that PLZF is modified by SUMO-1 conjugation and that this modification regulates the biological functions of PLZF.
Highlights
Promyelocytic leukemia zinc finger protein (PLZF)1 is a sequence-specific DNA-binding transcriptional regulator
We show that endogenous PLZF in human promyelocytic leukemia HL-60 cells is modified by conjugation with small ubiquitin-related modifier (SUMO)-1 and that PLZF colocalizes with SUMO-1 in the nucleus of transfected human embryonic kidney 293T cells
This observation suggested that the 96 kDa protein is a modified form of PLZF, and the difference in size between the two proteins was consistent with the addition of one molecule of SUMO-1
Summary
Promyelocytic leukemia zinc finger protein (PLZF)1 is a sequence-specific DNA-binding transcriptional regulator. Promyelocytic leukemia zinc finger (PLZF) protein is a sequence-specific DNA-binding protein that represses the transcriptional activity of target genes such as those for cyclin A and the interleukin-3 receptor ␣ chain. A luciferase reporter gene assay suggested that SUMO-1 modification of this residue is required for transcriptional repression by PLZF, and an electrophoretic mobility shift assay showed that this modification increases the DNA binding activity of PLZF.
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