FAT10, a ubiquitin-independent signal for proteasomal degradation

Mark Steffen Hipp, Birte Kalveram, Shahri Raasi, Marcus Groettrup, Gunter Schmidtke

Research output: Contribution to journalArticle

133 Citations (Scopus)

Abstract

FAT10 is a small ubiquitin-like modifier that is encoded in the major histocompatibility complex and is synergistically inducible by tumor necrosis factor alpha and gamma interferon. It is composed of two ubiquitin-like domains and possesses a free C-terminal diglycine motif that is required for the formation of FAT10 conjugates. Here we show that unconjugated FAT10 and a FAT10 conjugate were rapidly degraded by the proteasome at a similar rate. Fusion of FAT10 to the N terminus of very long-lived proteins enhanced their degradation rate as potently as fusion with ubiquitin did. FAT10-green fluorescent protein fusion proteins were not cleaved but entirely degraded, suggesting that FAT10-specific deconjugating enzymes were not present in the analyzed cell lines. Interestingly, the prevention of ubiquitylation of FAT10 by mutation of all lysines or by expression in ubiquitylation-deficient cells did not affect FAT10 degradation. Thus, conjugation with FAT10 is an alternative and ubiquitin-independent targeting mechanism for degradation by the proteasome, which, in contrast to polyubiquitylation, is cytokine inducible and irreversible.

Original languageEnglish (US)
Pages (from-to)3483-3491
Number of pages9
JournalMolecular and Cellular Biology
Volume25
Issue number9
DOIs
StatePublished - May 2005
Externally publishedYes

Fingerprint

Ubiquitin
Ubiquitination
Proteasome Endopeptidase Complex
Glycylglycine
Green Fluorescent Proteins
Major Histocompatibility Complex
Interferon-alpha
Lysine
Interferon-gamma
Proteins
Tumor Necrosis Factor-alpha
Cytokines
Cell Line
Mutation
Enzymes

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Hipp, M. S., Kalveram, B., Raasi, S., Groettrup, M., & Schmidtke, G. (2005). FAT10, a ubiquitin-independent signal for proteasomal degradation. Molecular and Cellular Biology, 25(9), 3483-3491. https://doi.org/10.1128/MCB.25.9.3483-3491.2005

FAT10, a ubiquitin-independent signal for proteasomal degradation. / Hipp, Mark Steffen; Kalveram, Birte; Raasi, Shahri; Groettrup, Marcus; Schmidtke, Gunter.

In: Molecular and Cellular Biology, Vol. 25, No. 9, 05.2005, p. 3483-3491.

Research output: Contribution to journalArticle

Hipp, MS, Kalveram, B, Raasi, S, Groettrup, M & Schmidtke, G 2005, 'FAT10, a ubiquitin-independent signal for proteasomal degradation', Molecular and Cellular Biology, vol. 25, no. 9, pp. 3483-3491. https://doi.org/10.1128/MCB.25.9.3483-3491.2005
Hipp, Mark Steffen ; Kalveram, Birte ; Raasi, Shahri ; Groettrup, Marcus ; Schmidtke, Gunter. / FAT10, a ubiquitin-independent signal for proteasomal degradation. In: Molecular and Cellular Biology. 2005 ; Vol. 25, No. 9. pp. 3483-3491.
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