Spermidine/spermine-N1-acetyltransferase 2 is an essential component of the ubiquitin ligase complex that regulates hypoxia-inducible factor 1alpha.

Abstract

Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor that functions as a master regulator of oxygen homeostasis. The HIF-1alpha subunit is subjected to O(2)-dependent prolyl hydroxylation leading to ubiquitination by the von Hippel-Lindau protein (VHL)-Elongin C ubiquitin-ligase complex and degradation by the 26 S proteasome. In this study, we demonstrate that spermidine/spermine-N(1)-acetyltransferase (SSAT) 2 plays an essential role in this process. SSAT2 binds to HIF-1alpha, VHL, and Elongin C and promotes ubiquitination of hydroxylated HIF-1alpha by stabilizing the interaction of VHL and Elongin C. Multivalent interactions by SSAT2 provide a mechanism to ensure efficient complex formation, which is necessary for the extremely rapid ubiquitination and degradation of HIF-1alpha that is observed in oxygenated cells.

• Authors: Jin Hyen Baek, Ye V Liu, Karin R McDonald, Jacob B Wesley, Maimon E Hubbi, Hweejo Byun, Gregg L Semenza
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 282 Issue 32 Pg. 23572-80 (Aug 10 2007) ISSN: 0021-9258 [Print] United States
• PMID: 17558023 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• ELOC protein, human
• Elongin
• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• Transcription Factors
• Acetyltransferases
• diamine N-acetyltransferase
• Ubiquitin-Protein Ligases
• Von Hippel-Lindau Tumor Suppressor Protein
• Glutathione Transferase
• Proteasome Endopeptidase Complex
• ATP dependent 26S protease
• VHL protein, human
• Oxygen

Topics

• Acetyltransferases (chemistry, physiology)
• Cell Line
• Elongin
• Genetic Vectors
• Glutathione Transferase (metabolism)
• Humans
• Hypoxia
• Hypoxia-Inducible Factor 1, alpha Subunit (chemistry, physiology)
• Models, Biological
• Oxygen (metabolism)
• Proteasome Endopeptidase Complex (chemistry)
• Protein Binding
• Transcription Factors (chemistry)
• Two-Hybrid System Techniques
• Ubiquitin-Protein Ligases (metabolism)
• Von Hippel-Lindau Tumor Suppressor Protein (chemistry)