Premium
Neddylation modification of ribosomal protein RPS27L or RPS27 by MDM2 or NEDP1 regulates cancer cell survival
Author(s) -
Xiong Xiufang,
Cui Danrui,
Bi Yanli,
Sun Yi,
Zhao Yongchao
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202000530rrr
Subject(s) - neddylation , nedd8 , technoscience , ubiquitin , microbiology and biotechnology , ribosomal protein , ubiquitin ligase , biology , gene knockdown , cancer cell , cancer , ribosome , apoptosis , biochemistry , genetics , gene , rna , social science , sociology
Neddylation plays a distinct role in stabilization of a subset of ribosomal proteins. Whether the family of ribosomal proteins S27 (RPS27 and RPS27‐like) is subjected to neddylation regulation with associated biological consequence is totally unknown. Here, we report that both family members are subjected to neddylation by MDM2 E3 ubiquitin ligase, and deneddylation by NEDP1. Blockage of neddylation with MLN4924, a small molecule inhibitor of neddylation‐activating enzyme, destabilizes RPS27L and RPS27 by shortening their protein half‐lives. Biologically, knockdown of RPS27L and RPS27 sensitizes, whereas ectopic expression of RPS27L and RPS27 desensitizes cancer cells to MLN4924‐induced apoptosis. Taken together, our study demonstrates that neddylation stabilizes RPS27L and RPS27 to confer the survival of cancer cells.