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

Anna V. Kuznetsova, Jaroslaw Meller, Phillip O. Schnell, James A. Nash, Monika L. Ignacak, Yolanda Sanchez, Joan W. Conaway, Ronald C. Conaway, Maria F. Czyzyk-Krzeska

Research output: Contribution to journalArticlepeer-review

178 Scopus citations

Abstract

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 hyper- phosphorylated 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 1α (HIF-1α) that binds von Hippel-Lindau tumor suppressor protein (pVHL). pVHL confers substrate specificity to the E3 ligase complex, which ubiquitinates HIF-α 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.

Original languageEnglish (US)
Pages (from-to)2706-2711
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number5
DOIs
StatePublished - Mar 4 2003
Externally publishedYes

ASJC Scopus subject areas

  • General

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