ArticleMolecular cancer therapeutics2008
UBE1L represses PML/RAR{alpha} by targeting the PML domain for ISG15ylation.
Article in Molecular cancer therapeutics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 58 citations in OpenAlex.
- Identification of UBA7 expression downregulation in myelodysplastic neoplasm with SF3B1 mutations.Scientific reports · 2025Article
- ISGylation: is our genome yearning for such a modification?Acta biochimica et biophysica Sinica · 2025Review
- The PML hub: An emerging actor of leukemia therapies.The Journal of experimental medicine · 2023Article
- Deneddylation of PML/RARα reconstructs functional PML nuclear bodies via orchestrating phase separation to eradicate APL.Cell death and differentiation · 2022Article
- ISG15 deficiency restricts HIV-1 infection.PLoS pathogens · 2022Article
- ISG15 and ISGylation in Human Diseases.Cells · 2022Review
- Acute Myeloid Leukemia-Related Proteins Modified by Ubiquitin and Ubiquitin-like Proteins.International journal of molecular sciences · 2022Review
- Deubiquitinases in hematological malignancies.Biomarker research · 2021Review
- The Ubiquitin-Specific Peptidase USP18 Promotes Lipolysis, Fatty Acid Oxidation, and Lung Cancer Growth.Molecular cancer research : MCR · 2021Article
- Crosstalk Between SUMO and Ubiquitin-Like Proteins: Implication for Antiviral Defense.Frontiers in cell and developmental biology · 2021Review
- OGP46 Induces Differentiation of Acute Myeloid Leukemia Cells via Different Optimal Signaling Pathways.Frontiers in cell and developmental biology · 2021Article
- Review
- Inhibition of UBE2L6 attenuates ISGylation and impedes ATRA-induced differentiation of leukemic cells.Molecular oncology · 2020Article
- ISG15 in antiviral immunity and beyond.Nature reviews. Microbiology · 2018Review
- Evidence for the ISG15-Specific Deubiquitinase USP18 as an Antineoplastic Target.Cancer research · 2018Review
- PML: Regulation and multifaceted function beyond tumor suppression.Cell & bioscience · 2018Review
- Deubiquitinase USP18 Loss Mislocalizes and Destabilizes KRAS in Lung Cancer.Molecular cancer research : MCR · 2017Article
- The ISG15-specific protease USP18 regulates stability of PTEN.Oncotarget · 2017Article
- Positive feedback regulation of p53 transactivity by DNA damage-induced ISG15 modification.Nature communications · 2016Article
- Emerging roles for immunomodulatory functions of free ISG15.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2013Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
Acute promyelocytic leukemia (APL) is characterized by expression of promyelocytic leukemia (PML)/retinoic acid (RA) receptor alpha (RARalpha) protein and all-trans-RA-mediated clinical remissions. RA treatment can confer PML/RARalpha degradation, overcoming dominant-negative effects of this oncogenic protein. The present study uncovered independent retinoid degradation mechanisms, targeting different domains of PML/RARalpha. RA treatment is known to repress PML/RARalpha and augment ubiquitin-activating enzyme-E1-like (UBE1L) protein expression in NB4-S1 APL cells. We previously reported RA-induced UBE1L and the IFN-stimulated gene, 15-kDa protein ISG15ylation in APL cells. Whether the ubiquitin-like protein ISG15 directly conjugates with PML/RARalpha was not explored previously and is examined in this study. Transient transfection experiments with different PML/RARalpha domains revealed that RA treatment preferentially down-regulated the RARalpha domain, whereas UBE1L targeted the PML domain for repression. As expected, ubiquitin-specific protease 18 (UBP43/USP18), the ISG15 deconjugase, opposed UBE1L but not RA-dependent PML/RARalpha degradation. In contrast, the proteasomal inhibitor, N-acetyl-leucinyl-leucinyl-norleucinal, inhibited both UBE1L- and RA-mediated PML/RARalpha degradation. Notably, UBE1L induced ISG15ylation of the PML domain of PML/RARalpha, causing its repression. These findings confirmed that RA triggers PML/RARalpha degradation through different domains and distinct mechanisms. Taken together, these findings advance prior work by establishing two pathways converge on the same oncogenic protein to cause its degradation and thereby promote antineoplastic effects. The molecular pharmacologic implications of these findings are discussed.
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