| First Author | Zhu J | Year | 2005 |
| Journal | Cancer Cell | Volume | 7 |
| Issue | 2 | Pages | 143-53 |
| PubMed ID | 15710327 | Mgi Jnum | J:95945 |
| Mgi Id | MGI:3528124 | Doi | 10.1016/j.ccr.2005.01.005 |
| Citation | Zhu J, et al. (2005) A sumoylation site in PML/RARA is essential for leukemic transformation. Cancer Cell 7(2):143-153 |
| abstractText | 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. |
