Related Experiment Video

Updated: Jul 6, 2026

Rapid Analysis of Chromosome Aberrations in Mouse B Lymphocytes by PNA-FISH
07:54

Rapid Analysis of Chromosome Aberrations in Mouse B Lymphocytes by PNA-FISH

Published on: August 19, 2014

RNF4 is a poly-SUMO-specific E3 ubiquitin ligase required for arsenic-induced PML degradation

Michael H Tatham1, Marie-Claude Geoffroy, Linnan Shen

  • 1Wellcome Trust Centre for Gene Regulation and Expression, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK.

Nature Cell Biology
|April 15, 2008
PubMed

Insights

RNF4 targets poly-SUMOylated proteins for degradation. In acute promyelocytic leukaemia, RNF4 is crucial for arsenic-induced PML degradation, highlighting SUMO chains as degradation signals.

Area of Science:

  • Molecular Biology
  • Cellular Biology
  • Oncology

Background:

  • Acute promyelocytic leukaemia (APL) involves PML-RAR fusion protein.
  • Arsenic therapy for APL induces PML modification and degradation.
  • The role of ubiquitin E3 ligases in SUMO-mediated protein degradation is emerging.

Purpose of the Study:

  • To investigate the role of RNF4 in targeting poly-SUMOylated proteins for degradation.
  • To determine if RNF4 mediates the arsenic-induced degradation of PML in APL.

Main Methods:

  • RNF4 depletion and proteasome inhibition experiments.
  • In vitro ubiquitination assays.
  • Immunofluorescence and Western blot analysis of PML and SUMOylated proteins.

Main Results:

  • RNF4 depletion or proteasome inhibition caused accumulation of polyubiquitinated and poly-SUMOylated proteins.
  • PML protein accumulated in RNF4-depleted cells and was ubiquitinated by RNF4 in a SUMO-dependent manner.
  • Arsenic failed to induce PML degradation in the absence of RNF4, leading to nuclear accumulation of SUMO-modified PML.

Conclusions:

  • Poly-SUMO chains act as distinct signals for protein degradation.
  • RNF4 is a key E3 ligase that targets poly-SUMOylated proteins, including PML, for ubiquitin-mediated proteolysis.
  • RNF4 is essential for the therapeutic efficacy of arsenic in APL by mediating PML degradation.

More Related Videos

Assays for the Degradation of Misfolded Proteins in Cells10:56

Assays for the Degradation of Misfolded Proteins in Cells

Published on: August 28, 2016

Related Concept Videos

Nonsense-mediated mRNA Decay02:27

Nonsense-mediated mRNA Decay

The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
Nuclear Export01:42

Nuclear Export

The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
Nuclear Export of mRNA02:31

Nuclear Export of mRNA

Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
Eukaryotic RNA Polymerases00:58

Eukaryotic RNA Polymerases

RNA Polymerase (RNAP) is conserved in all animals, with bacterial, archaeal, and eukaryotic RNAPs sharing significant sequence, structural, and functional similarities. Among the three eukaryotic RNAPs, RNA Polymerase II is most similar to bacterial RNAP in terms of both structural organization and folding topologies of the enzyme subunits. However, these similarities are not reflected in their mechanism of action.
All three eukaryotic RNAPs require specific transcription factors, of which the...
Transcriptional Regulation: Riboswitches01:23

Transcriptional Regulation: Riboswitches

Riboswitches are RNA elements that regulate gene expression by altering their secondary structures in response to specific effector molecules. These elements, located in the leader regions of certain mRNAs, act as transcriptional regulators by toggling between alternative conformations to control downstream gene expression. Riboswitch-mediated regulation is a precise mechanism for modulating biosynthetic pathways, as exemplified by the riboflavin biosynthesis pathway in Bacillus...