The promyelocytic leukemia zinc finger (PLZF) protein binds DNA in a high molecular weight complex associated with cdc2 kinase.
A binding site selection from a CpG island library for the promyelocytic leukemia zinc finger protein (PLZF) identified two high affinity PLZF binding sites. These sequences also bound RARalpha/PLZF, a fusion protein formed in chromosomal translocation t(11;17)(q23;q21) associated with acute promyelocytic leukemia. PLZF bound DNA as a slowly migrating complex with an estimated mol. wt of 600 kDa whose formation was dependent on the POZ/dimerization domain of PLZF. The PLZF-DNA complex was unable to form in the presence of cdc2 antibodies. A PLZF-cdc2 interaction was further demonstrated by co-immunoprecipitation and a biotin-streptavidin pull-down assay. PLZF is a phosphoprotein and immunoprecipi-tates with a cdc2-like kinase activity. The PLZF-DNA complex was abolished with the addition of a phosphatase. These studies suggest that the activity of PLZF, a regulator of the cell cycle, may be modulated by cell cycle proteins. RARalpha/PLZF did not complex with cdc2, this potentially contributing to its aberrant transcriptional properties and potential role in leukemo-genesis.
Ball
H J
HJ
Derald H. Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York, NY 10029, USA.
Melnick
A
A
Shaknovich
R
R
Kohanski
R A
RA
Licht
J D
JD
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D019556:COS Cells; D002880:Chromosomes, Human, Pair 11; D002886:Chromosomes, Human, Pair 17; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D008970:Molecular Weight; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D014157:Transcription Factors / Q000378:metabolism*; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; D046911:Macromolecular Substances; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D014157:Transcription Factors; C092037:ZBTB16 protein, human; D004247:DNA; D016203:CDC2 Protein Kinase