The PML nuclear bodies-associated protein TTRAP regulates ribosome biogenesis in nucleolar cavities upon proteasome inhibition

Cell Death Differ. 2012 Mar;19(3):488-500. doi: 10.1038/cdd.2011.118. Epub 2011 Sep 16.

Abstract

TRAF and TNF receptor-associated protein (TTRAP) is a multifunctional protein that can act in the nucleus as a 5'-tyrosyl DNA phosphodiesterase and in the cytoplasm as a regulator of cell signaling. In this paper we show that in response to proteasome inhibition TTRAP accumulates in nucleolar cavities in a promyelocytic leukemia protein-dependent manner. In the nucleolus, TTRAP contributes to control levels of ribosomal RNA precursor and processing intermediates, and this phenotype is independent from its 5'-tyrosyl DNA phosphodiesterase activity. Our findings suggest a previously unidentified function for TTRAP and nucleolar cavities in ribosome biogenesis under stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Nucleolus / genetics
  • Cell Nucleolus / metabolism*
  • DNA-Binding Proteins
  • HEK293 Cells
  • Humans
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Phosphoric Diester Hydrolases
  • Promyelocytic Leukemia Protein
  • Proteasome Endopeptidase Complex / genetics
  • Proteasome Endopeptidase Complex / metabolism
  • Proteasome Inhibitors*
  • RNA Processing, Post-Transcriptional / physiology*
  • RNA, Ribosomal / genetics
  • RNA, Ribosomal / metabolism*
  • Ribosomes / genetics
  • Ribosomes / metabolism*
  • Signal Transduction / physiology*
  • Stress, Physiological / physiology
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • DNA-Binding Proteins
  • Nuclear Proteins
  • Promyelocytic Leukemia Protein
  • Proteasome Inhibitors
  • RNA, Ribosomal
  • Transcription Factors
  • Tumor Suppressor Proteins
  • PML protein, human
  • Phosphoric Diester Hydrolases
  • TDP2 protein, human
  • Proteasome Endopeptidase Complex