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Degradation of FAT10 by the 26S proteasome is independent of ubiquitylation but relies on NUB1L
Author(s) -
Schmidtke Gunter,
Kalveram Birte,
Groettrup Marcus
Publication year - 2009
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.01.006
Subject(s) - proteasome , ubiquitin , degradation (telecommunications) , dihydrofolate reductase , protein degradation , chemistry , nedd8 , biochemistry , microbiology and biotechnology , biology , ubiquitin ligase , enzyme , gene , telecommunications , computer science
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.