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Retinoblastoma protein and the leukemia-associated PLZF transcription factor interact to repress target gene promoters.

Petrie, Kevin, Guidez, F, Zhu, J, Howell, L, Owen, G, Chew, Y P, Parks, S, Waxman, S, Licht, J, Mittnacht, S and Zelent, A (2008) Retinoblastoma protein and the leukemia-associated PLZF transcription factor interact to repress target gene promoters. Oncogene, 27 (39). pp. 5260-6. ISSN 1476-5594

Item Type: Article

Abstract

Translocations of the retinoic acid receptor-alpha (RARalpha) locus with the promyelocytic leukemia zinc-finger (PLZF) or PML genes lead to expression of oncogenic PLZF-RARalpha or PML-RARalpha fusion proteins, respectively. These fusion oncoproteins constitutively repress RARalpha target genes, in large part through aberrant recruitment of multiprotein co-repressor complexes. PML and PML-RARalpha 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 (poxvirus and zinc-finger, POZ) and DNA-binding (zinc-finger) domains. In addition, 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 of Rb with PML or E2F1, the PLZF-Rb interaction is not dependent on hypophosphorylation of Rb. These data are supported by chromatin immunoprecipitation analysis, which indicates that PLZF associates with the promoter region of CDC6, a known E2F/Rb target gene. Co-expression of PLZF and Rb results in enhancement of transcriptional repression of PLZF and E2F/Rb target genes, indicating functional co-operation between the two proteins. Both PLZF and Rb have been shown to function in stem cells and taken together these data suggest that interactions between PLZF and Rb could be important in stem cell biology.

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More Information

Depositing User: Kevin Petrie

Identifiers

Item ID: 12429
Identification Number: https://doi.org/10.1038/onc.2008.159
ISSN: 1476-5594
URI: http://sure.sunderland.ac.uk/id/eprint/12429
Official URL: https://www.nature.com/articles/onc2008159

Users with ORCIDS

ORCID for Kevin Petrie: ORCID iD orcid.org/0000-0002-9805-9152

Catalogue record

Date Deposited: 18 Aug 2020 12:58
Last Modified: 30 Sep 2020 10:48

Contributors

Author: Kevin Petrie ORCID iD
Author: F Guidez
Author: J Zhu
Author: L Howell
Author: G Owen
Author: Y P Chew
Author: S Parks
Author: S Waxman
Author: J Licht
Author: S Mittnacht
Author: A Zelent

University Divisions

Faculty of Health Sciences and Wellbeing > School of Medicine

Subjects

Sciences > Biomedical Sciences
Sciences > Health Sciences

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