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LNX functions as a RING type E3 ubiquitin ligase that targets the cell fate determinant Numb for ubiquitin‐dependent degradation
Author(s) -
Nie Jing,
McGill Melanie A.,
Dermer Matt,
Dho Sascha E.,
Wolting Cheryl D.,
McGlade C. Jane
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/21.1.93
Subject(s) - numb , ubiquitin ligase , pdz domain , ring finger domain , ring finger , biology , ubiquitin , ubiquitin protein ligases , microbiology and biotechnology , mutant , dna ligase , degron , proteasome , biochemistry , zinc finger , transcription factor , dna , gene
LNX is a RING finger and PDZ domain containing protein that interacts with the cell fate determinant Numb. To investigate the function of LNX, we tested its RING finger domain for ubiquitin ligase activity. The isolated RING finger domain was able to function as an E2‐dependent, E3 ubiquitin ligase in vitro and mutation of a conserved cysteine residue within the RING domain abolished its activity, indicating that LNX is the first described PDZ domain‐containing member of the E3 ubiquitin ligase family. We have identified Numb as a substrate of LNX E3 activity in vitro and in vivo . In addition to the RING finger, a region of LNX, including the Numb PTB domain‐binding site and the first PDZ domain, is required for Numb ubiquitylation. Expression of wild‐type but not mutant LNX causes proteasome‐dependent degradation of Numb and can enhance Notch signalling. These results suggest that the levels of mammalian Numb protein and therefore, by extension, the processes of asymmetric cell division and cell fate determination may be regulated by ubiquitin‐dependent proteolysis.