Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 100, Issue 5, Pages 2706-2711Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0436037100
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- NHLBI NIH HHS [R01 HL066312, HL66312, R01 HL058687] Funding Source: Medline
- PHS HHS [L58687] Funding Source: Medline
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The transition from transcription initiation to elongation involves phosphorylation of the large subunit (Rpb1) of RNA polymerase 11 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 11 (Rpb6) that share sequence and structural similarity with the domain of hypoxia-inducible transcription factor 1alpha (HIF-1alpha) 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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