Von Hippel-Lindau Protein Binds Hyperphosphorylated Large Subunit of RNA Polymerase II Through a Proline Hydroxylation Motif and Targets It for Ubiquitination

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2003 Feb 27

PMID 12604794

Citations 86

Authors

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

Affiliations

Soon will be listed here.

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 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.

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