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

Abstract 

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.

Abbreviations: AZ, antizyme, DHFR, dihydrofolate reductase, NUB1L, NEDD8 ultimate buster 1-long, ODC, ornithine decarboxylase

Keywords: Ubiquitin, FAT10, 26S proteasome, NUB1L, Degradation