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Nucleolar control by a non‐apoptotic p53‐caspases‐deubiquitinylase axis promotes resistance to bacterial infection
Author(s) -
Chen PoHsiang,
Chen YiTung,
Chu TaiYing,
Ma TianHsiang,
Wu MeiHsuan,
Lin HsiHsien,
Chang YuSun,
Tan Bertrand ChinMing,
Lo Szecheng J.
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.201901959r
Subject(s) - fibrillarin , biology , nucleolus , microbiology and biotechnology , caenorhabditis elegans , innate immune system , downregulation and upregulation , gene knockdown , caspase , apoptosis , gene , programmed cell death , genetics , immune system , cytoplasm
The nucleolus is best known for its cellular role in regulating ribosome production and growth. More recently, an unanticipated role for the nucleolus in innate immunity has recently emerged whereby downregulation of fibrillarin and nucleolar contraction confers pathogen resistance across taxa. The mechanism of this downregulation, however, remains obscure. Here we report that rather than fibrillarin itself being the proximal factor in this pathway, the key player is a fibrillarin‐stabilizing deubiquitinylase USP‐33. This was discovered by a candidate‐gene search of Caenorhabditis elegans in which CED‐3 caspase was revealed to execute targeted cleavage of USP‐33, thus destabilizing fibrillarin. We also showed that cep‐1 and ced‐3 mutant worms altered nucleolar size and decreased antimicrobial peptide gene, spp‐1 , expression rendering susceptibility to bacterial infection. These phenotypes were reversed by usp‐33 knockdown, thus linking the CEP‐1‐CED‐3‐USP‐33 pathway with nucleolar control and resistance to bacterial infection in worms. Parallel experiments with the human analogs of caspases and USP36 revealed similar roles in coordinating these two processes. In summary, our work outlined a conserved cascade that connects cell death signaling to nucleolar control and innate immune response.