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The role of PLZF in the transcriptional repression of the p21CIP1 gene

The PLZF which is involved in rare cases of acute promyelocytic leukemia, is a POK family transcription factor containing nine Krüppel‐like C‐terminal Cys2–His2 zinc finger motifs and an N‐terminus BTB/POZ‐domain. PLZF plays important roles in myeloid cell growth, differentiation, and apoptosis. We investigated whether PLZF can regulate genes of ARF‐MDM2‐p53‐p21 regulatory pathway, which is important in cell cycle regulation and oncogenesis. We found that p21 gene, an ARF/p53 downstream cell cycle regulator gene, is the molecular target of PLZF. We dissected the molecular mechanism of transcription repression of p21 gene by PLZF. We found that PLZF directly bound onto the proximal Sp1 binding GC‐box elements 5/6 and the distal p53 binding elements of p21 promoter, and thereby it blocked transcriptional activation by Sp1 and p53. Our data also suggested that PLZF represses p21 gene by recruitment of corepressor‐HDAC complex recruited onto the binding sites via PLZF. PLZF caused cellular transformation, promoted cell cycle proliferation, and also increased the number of cells in S‐phase probably by affecting the gene transcription of p53 pathway.