High impact information on SEL1

• Two new papers reveal that the Ubx2 protein physically links ER-membrane-integrated ubiquitin ligases to Cdc48p, and that it is essential for degradation of substrates that are ubiquitylated at the cytoplasmic face of the ER [1].
• Membrane-bound Ubx2 recruits Cdc48 to ubiquitin ligases and their substrates to ensure efficient ER-associated protein degradation [2].
• Here we show that the UBX domain protein Ubx2 is an integral ER membrane protein that recruits Cdc48 to the ER [2].
• Structure, function, and expression of SEL-1, a negative regulator of LIN-12 and GLP-1 in C. elegans [3].
• The two major yeast UBX domain proteins, Shp1 and Ubx2, possess a ubiquitin-binding UBA domain and interact with ubiquitylated proteins in vivo [4].

Biological context of SEL1

• SEL1 isolated from S. cerevisiae suppressed the super-secretion phenotype in K. lactis klsel1 strain, likewise homologous KlSEL1 [5].
• These results suggest that HRD1 and SEL1 are up-regulated by the UPR and contribute to protection against the ER stress-induced cell death by degrading unfolded proteins accumulated in the ER [6].

Physical interactions of SEL1

• The membrane protein Ubx2 contains a UBX domain that interacts with Cdc48 and an additional UBA domain [7].

Other interactions of SEL1

• Ubx2 links the Cdc48 complex to ER-associated protein degradation [7].
• Thus, a complex comprising the AAA ATPase, a ubiquitin ligase and the recruitment factor Ubx2 has a central role in ER-associated proteolysis [7].

References