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

Hyen Baek Jin, Ye V. Liu, Karin R. McDonald, Jacob B. Wesley, Maimon E. Hubbi, Hweejo Byun, Gregg L Semenza

Research output: Contribution to journalArticle

Abstract

Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor that functions as a master regulator of oxygen homeostasis. The HIF-1α subunit is subjected to O2-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-N1-acetyltransferase (SSAT) 2 plays an essential role in this process. SSAT2 binds to HIF-1α, VHL, and Elongin C and promotes ubiquitination of hydroxylated HIF-1α 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-1α that is observed in oxygenated cells.

Original languageEnglish (US)
Pages (from-to)23572-23580
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number32
DOIs
StatePublished - Aug 10 2007

Fingerprint

Hypoxia-Inducible Factor 1
Acetyltransferases
Spermidine
Spermine
Ligases
Ubiquitin
Ubiquitination
Protein C
Degradation
Hydroxylation
Proteasome Endopeptidase Complex
Homeostasis
Transcription Factors
diamine N-acetyltransferase
Oxygen
elongin
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Spermidine/Spermine-N1-acetyltransferase 2 is an essential component of the ubiquitin ligase complex that regulates hypoxia-inducible factor 1α. / Jin, Hyen Baek; Liu, Ye V.; McDonald, Karin R.; Wesley, Jacob B.; Hubbi, Maimon E.; Byun, Hweejo; Semenza, Gregg L.

In: Journal of Biological Chemistry, Vol. 282, No. 32, 10.08.2007, p. 23572-23580.

Research output: Contribution to journalArticle

Jin, Hyen Baek ; Liu, Ye V. ; McDonald, Karin R. ; Wesley, Jacob B. ; Hubbi, Maimon E. ; Byun, Hweejo ; Semenza, Gregg L. / Spermidine/Spermine-N1-acetyltransferase 2 is an essential component of the ubiquitin ligase complex that regulates hypoxia-inducible factor 1α. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 32. pp. 23572-23580.
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abstract = "Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric transcription factor that functions as a master regulator of oxygen homeostasis. The HIF-1α subunit is subjected to O2-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-N1-acetyltransferase (SSAT) 2 plays an essential role in this process. SSAT2 binds to HIF-1α, VHL, and Elongin C and promotes ubiquitination of hydroxylated HIF-1α 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-1α that is observed in oxygenated cells.",
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AU - Wesley, Jacob B.

AU - Hubbi, Maimon E.

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