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The promyelocytic leukemia protein PML interacts with the proline-rich homeodomain protein PRH: a RING may link hematopoiesis and growth control

Oncogene volume 18, pages 7091–7100 (1999)Cite this article

Abstract

Acute promyelocytic leukemia (APL) is characterized by a block in myeloid cell differentiation. As a result of a chromosomal translocation in these patients, the promyelocytic leukemia protein PML is disrupted as are the nuclear bodies it forms. Disruption of PML and PML nuclear bodies in APL is linked to a loss of growth control and subsequent leukemogenesis. PML contains a zinc-binding domain known as the RING which is required for formation of these bodies. Using yeast 2-hybrid techniques, we found that PML and a related RING protein, Z, bind the proline rich homeodomain protein (PRH) through their RING domains. Previous reports indicate that PRH functions in hematopoiesis and may act as a transcriptional repressor. Our data indicate that PML and Z both bind the repressor domain of PRH and are the first protein partners reported for PRH. We observe that PRH has a punctate pattern in both the nucleus and cytoplasm of chronic myelogenous leukemia K562 cells and in the APL cell line, NB4. Immunoprecipitation and co-localization studies indicate that PML and PRH interact in both cell lines. The effect on cell growth by PML and the hematopoietic actions of PRH raises the possibility that the interaction between PML and PRH represents a link between growth control and hematopoiesis.

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Acknowledgements

The mAb 5E10 antibody was a kind gift of L de Jong. We are grateful for technical assistance and advice from Graeme W Carlile and Melanie J Dobson and for critical reading of the manuscript by Ari Melnick. KLB Borden acknowledges support from MRC MT-13608, RO1 CA80728-01 and Leukemia Research Foundation.

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  1. Zeki Topcu

    Present address: Faculty of Pharmacy, Ege University, Izmir, Turkey

Authors and Affiliations

  1. Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, 10029, NY, USA

    Zeki Topcu & Katherine LB Borden

  2. Indiana Cancer Research Institute, Indianopolis, 46202 – 5254, Indiana, IN, USA

    David L Mack & Robert A Hromas

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  2. David L Mack
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Topcu, Z., Mack, D., Hromas, R. et al. The promyelocytic leukemia protein PML interacts with the proline-rich homeodomain protein PRH: a RING may link hematopoiesis and growth control. Oncogene 18, 7091–7100 (1999). https://doi.org/10.1038/sj.onc.1203201

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