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Updated: Aug 12, 2026

In Vivo Detection and Analysis of Rb Protein SUMOylation in Human Cells
Published on: November 2, 2017
A sumoylation site in PML/RARA is essential for leukemic transformation
Jun Zhu1, Jun Zhou, Laurent Peres
1CNRS UPR 9051, laboratoire associé N11 du comité de Paris de la Ligue contre le Cancer, affilié à l'Université de Paris VII, Hôpital St. Louis, 1 avenue Claude Vellefaux, 75475 Paris, Cedex 10, France.
Abstract:
Pathogenesis of acute promyelocytic leukemia (APL) has been proposed to involve transcriptional repression through enhanced corepressors binding onto RARA moieties of PML/RARA homodimers. Unexpectedly, we show that the K160 sumoylation site in the PML moiety of PML/RARA is required for efficient immortalization/differentiation arrest ex vivo, implying that RARA homodimerization is insufficient to fully immortalize primary hematopoietic progenitor cells. Similarly, PML/RARAK160R transgenic mice develop myeloproliferative syndromes, but never APL. The Daxx repressor no longer binds PML/RARAK160R, but fusion of these two proteins restores the differentiation block ex vivo. Thus, transcriptional repression dependent on a specific sumoylation site in PML is critical for the APL phenotype, while forced RARA dimerization could control expansion of the myeloid compartment.
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