• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Regulation and destabilization of HIF-1alpha by ARD1-mediated acetylation.

Hypoxia-inducible factor 1 (HIF-1) plays a central role in cellular adaptation to changes in oxygen availability. Recently, prolyl hydroxylation was identified as a key regulatory event that targets the HIF-1alpha subunit for proteasomal degradation via the pVHL ubiquitination complex. In this report, we reveal an important function for ARD1 in mammalian cells as a protein acetyltransferase by direct binding to HIF-1alpha to regulate its stability. We present further evidence showing that ARD1-mediated acetylation enhances interaction of HIF-1alpha with pVHL and HIF-1alpha ubiquitination, suggesting that the acetylation of HIF-1alpha by ARD1 is critical to proteasomal degradation. Therefore, we have concluded that the role of ARD1 in the acetylation of HIF-1alpha provides a key regulatory mechanism underlying HIF-1alpha stability.

Pubmed ID: 12464182

Authors

  • Jeong JW
  • Bae MK
  • Ahn MY
  • Kim SH
  • Sohn TK
  • Bae MH
  • Yoo MA
  • Song EJ
  • Lee KJ
  • Kim KW

Journal

Cell

Publication Data

November 27, 2002

Associated Grants

None

Mesh Terms

  • Acetylation
  • Amino Acid Sequence
  • Animals
  • Cell Hypoxia
  • Cell Line
  • Cell Line, Transformed
  • DNA-Binding Proteins
  • Endoribonucleases
  • Gene Expression Regulation
  • Green Fluorescent Proteins
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Luminescent Proteins
  • Mice
  • Molecular Sequence Data
  • Oxygen
  • Phosphoprotein Phosphatases
  • Protein Processing, Post-Translational
  • Protein Structure, Tertiary
  • RNA-Binding Proteins
  • Recombinant Proteins
  • Sequence Deletion
  • Sequence Homology, Amino Acid
  • Transcription Factors
  • Transcriptional Activation
  • Tumor Cells, Cultured