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von Hippel-Lindau protein binds hyperphosphorylated large subunit of RNA polymerase II through a proline hydroxylation motif and targets it for ubiquitination.

The transition from transcription initiation to elongation involves phosphorylation of the large subunit (Rpb1) of RNA polymerase II on the repetitive carboxyl-terminal domain. The elongating hyperphosphorylated Rpb1 is subject to ubiquitination, particularly in response to UV radiation and DNA-damaging agents. By using computer modeling, we identified regions of Rpb1 and the adjacent subunit 6 of RNA polymerase II (Rpb6) that share sequence and structural similarity with the domain of hypoxia-inducible transcription factor 1 alpha (HIF-1 alpha) that binds von Hippel-Lindau tumor suppressor protein (pVHL). pVHL confers substrate specificity to the E3 ligase complex, which ubiquitinates HIF-alpha and targets it for proteasomal degradation. In agreement with the computational model, we show biochemical evidence that pVHL specifically binds the hyperphosphorylated Rpb1 in a proline-hydroxylation-dependent manner, targeting it for ubiquitination. This interaction is regulated by UV radiation.

Pubmed ID: 12604794


  • Kuznetsova AV
  • Meller J
  • Schnell PO
  • Nash JA
  • Ignacak ML
  • Sanchez Y
  • Conaway JW
  • Conaway RC
  • Czyzyk-Krzeska MF


Proceedings of the National Academy of Sciences of the United States of America

Publication Data

March 4, 2003

Associated Grants

  • Agency: NHLBI NIH HHS, Id: HL66312
  • Agency: PHS HHS, Id: L58687

Mesh Terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Biotinylation
  • Blotting, Western
  • Cell Nucleus
  • DNA Damage
  • Ligases
  • Models, Molecular
  • Molecular Sequence Data
  • Oxygen
  • PC12 Cells
  • Phosphorylation
  • Precipitin Tests
  • Proline
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA Polymerase II
  • Rats
  • Sequence Homology, Amino Acid
  • Software
  • Substrate Specificity
  • Tumor Suppressor Proteins
  • Ubiquitin
  • Ubiquitin-Protein Ligases
  • Ultraviolet Rays
  • Von Hippel-Lindau Tumor Suppressor Protein