Degradation of FAT10 by the 26S proteasome is independent of ubiquitylation but relies on NUB1L

Gunter Schmidtke, Birte Kalveram, Marcus Groettrup

Research output: Contribution to journalArticle

43 Scopus citations


The ubiquitin-like modifier FAT10 targets proteins for degradation by the proteasome, a process accelerated by the UBL-UBA domain protein NEDD8 ultimate buster 1-long. Here, we show that FAT10-mediated degradation occurs independently of poly-ubiquitylation as purified 26S proteasome readily degraded FAT10-dihydrofolate reductase (DHFR) but not ubiquitin-DHFR in vitro. Interestingly, the 26S proteasome could only degrade FAT10-DHFR when NUB1L was present. Knock-down of NUB1L attenuated the degradation of FAT10-DHFR in intact cells suggesting that NUB1L determines the degradation rate of FAT10-linked proteins. In conclusion, our data establish FAT10 as a ubiquitin-independent but NUB1L-dependent targeting signal for proteasomal degradation.

Original languageEnglish (US)
Pages (from-to)591-594
Number of pages4
JournalFEBS Letters
Issue number3
StatePublished - Feb 4 2009



  • 26S proteasome
  • Degradation
  • FAT10
  • NUB1L
  • Ubiquitin

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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