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Arsenic-induced SUMO-dependent recruitment of RNF4 into PML nuclear bodies.

In acute promyelocytic leukemia (APL), the promyelocytic leukemia (PML) protein is fused to the retinoic acid receptor alpha (RAR). Arsenic is an effective treatment for this disease as it induces SUMO-dependent ubiquitin-mediated proteasomal degradation of the PML-RAR fusion protein. Here we analyze the nuclear trafficking dynamics of PML and its SUMO-dependent ubiquitin E3 ligase, RNF4 in response to arsenic. After administration of arsenic, PML immediately transits into nuclear bodies where it undergoes SUMO modification. This initial recruitment of PML into nuclear bodies is not dependent on RNF4, but RNF4 quickly follows PML into the nuclear bodies where it is responsible for ubiquitylation of SUMO-modified PML and its degradation by the proteasome. While arsenic restricts the mobility of PML, FRAP analysis indicates that RNF4 continues to rapidly shuttle into PML nuclear bodies in a SUMO-dependent manner. Under these conditions FRET studies indicate that RNF4 interacts with SUMO in PML bodies but not directly with PML. These studies indicate that arsenic induces the rapid reorganization of the cell nucleus by SUMO modification of nuclear body-associated PML and uptake of the ubiquitin E3 ligase RNF4 leading to the ubiquitin-mediated degradation of PML.

Pubmed ID: 20943951


  • Geoffroy MC
  • Jaffray EG
  • Walker KJ
  • Hay RT


Molecular biology of the cell

Publication Data

December 30, 2010

Associated Grants

  • Agency: Cancer Research UK, Id:

Mesh Terms

  • Arsenic
  • Blotting, Western
  • Fluorescent Antibody Technique
  • HeLa Cells
  • Humans
  • Immunoprecipitation
  • Nuclear Proteins
  • Oncogene Proteins, Fusion
  • Proteasome Endopeptidase Complex
  • Receptors, Retinoic Acid
  • Reverse Transcriptase Polymerase Chain Reaction
  • Small Ubiquitin-Related Modifier Proteins
  • Transcription Factors
  • Tumor Suppressor Proteins
  • Ubiquitin
  • Ubiquitin-Protein Ligases
  • Ubiquitination