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

doi:10.1074/jbc.M703504200

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

45 Scopus citations

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 language	English (US)
Pages (from-to)	23572-23580
Number of pages	9
Journal	Journal of Biological Chemistry
Volume	282
Issue number	32
DOIs	https://doi.org/10.1074/jbc.M703504200
State	Published - Aug 10 2007

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Cell Biology

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

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.",

author = "Jin, {Hyen Baek} and Liu, {Ye V.} and McDonald, {Karin R.} and Wesley, {Jacob B.} and Hubbi, {Maimon E.} and Hweejo Byun and Semenza, {Gregg L.}",

year = "2007",

month = aug,

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doi = "10.1074/jbc.M703504200",

language = "English (US)",

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T1 - Spermidine/Spermine-N1-acetyltransferase 2 is an essential component of the ubiquitin ligase complex that regulates hypoxia-inducible factor 1α

AU - Jin, Hyen Baek

AU - Liu, Ye V.

AU - McDonald, Karin R.

AU - Wesley, Jacob B.

AU - Hubbi, Maimon E.

AU - Byun, Hweejo

AU - Semenza, Gregg L.

PY - 2007/8/10

Y1 - 2007/8/10

N2 - 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.

AB - 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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JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

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ER -

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

Abstract

ASJC Scopus subject areas

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