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Abstract 1240: Retinoblastoma Protein and the Leukemia-Associated PLZF Transcription Factor Interact To Repress Target Gene Promoters.

Petrie, Kevin R., Guidez, Fabien, Zhu, Jun, Owen, Gareth, Chew, Yat Peng, Waxman, Samuel, Licht, Jonathan D., Mittnacht, Sibylle and Arthur, Zelent (2007) Abstract 1240: Retinoblastoma Protein and the Leukemia-Associated PLZF Transcription Factor Interact To Repress Target Gene Promoters. Blood, 110 (11). p. 1240. ISSN 0006-4971

Item Type: Article


Translocations of the retinoic acid receptor alpha (RARA) locus with the PLZF or PML genes lead to expression of oncogenic PLZF-RARα or PML-RARα fusion proteins, respectively. These fusion oncoproteins constitutively repress RARα target genes, in large part through aberrant recruitment of multiprotein co-repressor complexes. PML and PML-RARα have previously been shown to associate with the retinoblastoma (Rb) tumour suppressor protein in its hypophosphorylated state. Here we demonstrate that PLZF also interacts with Rb in vitro and in vivo. The interaction between PLZF and Rb is mediated through the Rb pocket and the region of PLZF that lies between its transcriptional repression (POZ) and DNA binding (zinc-finger) domains. Additionally, Rb can simultaneously interact with PLZF and the E2F1 S phase-inducing transcription factor, suggesting that these proteins can exist in the same multiprotein complex. In contrast to the interaction between PML or E2F1 with Rb, the PLZF-Rb interaction is not dependent on hypophosphorylation of Rb. The interaction between PLZF and Rb is further underlined by chromatin immunoprecipitation analysis of PLZF binding to genomic DNA, which shows that PLZF associates with genes controlling cell proliferation known to be regulated by Rb and E2F (for example cdc6). Co-expression of PLZF and Rb results in enhancement of transcriptional repression of PLZF and E2F target genes, indicating functional co-operation between the two proteins. Both PLZF and Rb have been shown to have roles in stem cell biology and, taken together, these data provide a plausible scenario in which interactions between PLZF and Rb function in stem cell commitment or maintenance and self-renewal. The oncogenic PLZF-RARα fusion also interacts with Rb, suggesting that deregulation of Rb function may be a factor in the molecular pathogenesis of PLZF-RARα associated acute promyelocytic leukemia.

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Uncontrolled Keywords: candidate disease gene, leukemia, retinoblastoma protein, transcription factor, oncogenes, progressive multifocal leukoencephalopathy, dna, retinoic acid receptor alpha, acute promyelocytic leukemia, complex
Depositing User: Kevin Petrie


Item ID: 15813
Identification Number:
ISSN: 0006-4971
Official URL:

Users with ORCIDS

ORCID for Kevin R. Petrie: ORCID iD

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Date Deposited: 22 Mar 2023 15:30
Last Modified: 22 Mar 2023 15:30


Author: Kevin R. Petrie ORCID iD
Author: Fabien Guidez
Author: Jun Zhu
Author: Gareth Owen
Author: Yat Peng Chew
Author: Samuel Waxman
Author: Jonathan D. Licht
Author: Sibylle Mittnacht
Author: Zelent Arthur

University Divisions

Faculty of Health Sciences and Wellbeing > School of Medicine


Sciences > Biomedical Sciences

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