RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation
- PMID: 18408734
- DOI: 10.1038/ncb1716
RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation
Abstract
In acute promyelocytic leukaemia (APL), the promyelocytic leukaemia (PML) protein is fused to the retinoic acid receptor alpha (RAR). This disease can be treated effectively with arsenic, which induces PML modification by small ubiquitin-like modifiers (SUMO) and proteasomal degradation. Here we demonstrate that the RING-domain-containing ubiquitin E3 ligase, RNF4 (also known as SNURF), targets poly-SUMO-modified proteins for degradation mediated by ubiquitin. RNF4 depletion or proteasome inhibition led to accumulation of mixed, polyubiquitinated, poly-SUMO chains. PML protein accumulated in RNF4-depleted cells and was ubiquitinated by RNF4 in a SUMO-dependent fashion in vitro. In the absence of RNF4, arsenic failed to induce degradation of PML and SUMO-modified PML accumulated in the nucleus. These results demonstrate that poly-SUMO chains can act as discrete signals from mono-SUMOylation, in this case targeting a poly-SUMOylated substrate for ubiquitin-mediated proteolysis.
Comment in
-
Marked for death.Nat Cell Biol. 2008 May;10(5):507-9. doi: 10.1038/ncb0508-507. Nat Cell Biol. 2008. PMID: 18454129 No abstract available.
Similar articles
-
Arsenic degrades PML or PML-RARalpha through a SUMO-triggered RNF4/ubiquitin-mediated pathway.Nat Cell Biol. 2008 May;10(5):547-55. doi: 10.1038/ncb1717. Epub 2008 Apr 13. Nat Cell Biol. 2008. PMID: 18408733
-
Arsenic-induced SUMO-dependent recruitment of RNF4 into PML nuclear bodies.Mol Biol Cell. 2010 Dec;21(23):4227-39. doi: 10.1091/mbc.E10-05-0449. Epub 2010 Oct 13. Mol Biol Cell. 2010. PMID: 20943951 Free PMC article.
-
Role of SUMO in RNF4-mediated promyelocytic leukemia protein (PML) degradation: sumoylation of PML and phospho-switch control of its SUMO binding domain dissected in living cells.J Biol Chem. 2009 Jun 12;284(24):16595-16608. doi: 10.1074/jbc.M109.006387. Epub 2009 Apr 20. J Biol Chem. 2009. PMID: 19380586 Free PMC article.
-
Pathways of retinoic acid- or arsenic trioxide-induced PML/RARalpha catabolism, role of oncogene degradation in disease remission.Oncogene. 2001 Oct 29;20(49):7257-65. doi: 10.1038/sj.onc.1204852. Oncogene. 2001. PMID: 11704854 Review.
-
New insights into the cytoplasmic function of PML.Histol Histopathol. 2007 Aug;22(8):937-46. doi: 10.14670/HH-22.937. Histol Histopathol. 2007. PMID: 17503350 Review.
Cited by
-
A comprehensive compilation of SUMO proteomics.Nat Rev Mol Cell Biol. 2016 Sep;17(9):581-95. doi: 10.1038/nrm.2016.81. Epub 2016 Jul 20. Nat Rev Mol Cell Biol. 2016. PMID: 27435506
-
The increasing complexity of the ubiquitin code.Nat Cell Biol. 2016 May 27;18(6):579-86. doi: 10.1038/ncb3358. Nat Cell Biol. 2016. PMID: 27230526 Review.
-
Ubiquitylation in DNA double-strand break repair.DNA Repair (Amst). 2021 Jul;103:103129. doi: 10.1016/j.dnarep.2021.103129. Epub 2021 May 7. DNA Repair (Amst). 2021. PMID: 33990032 Free PMC article.
-
Gold nanoparticles as a platform for creating a multivalent poly-SUMO chain inhibitor that also augments ionizing radiation.Proc Natl Acad Sci U S A. 2012 Mar 13;109(11):4092-7. doi: 10.1073/pnas.1109131109. Epub 2012 Mar 2. Proc Natl Acad Sci U S A. 2012. PMID: 22388745 Free PMC article.
-
Azacytidine sensitizes acute myeloid leukemia cells to arsenic trioxide by up-regulating the arsenic transporter aquaglyceroporin 9.J Hematol Oncol. 2015 May 8;8:46. doi: 10.1186/s13045-015-0143-3. J Hematol Oncol. 2015. PMID: 25953102 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
