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The ubiquitin‐interacting motifs of 26S proteasome subunit S5a induces the cellular vacuolization and ER stress in A549 lung cancer cells
Author(s) -
Elangovan Muthukumar,
Yoo Yung Joon
Publication year - 2008
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/fasebj.22.1_supplement.793.2
Subject(s) - vacuolization , a549 cell , biology , proteasome , microbiology and biotechnology , ubiquitin , programmed cell death , cell cycle , ectopic expression , cell , cell culture , apoptosis , genetics , endocrinology , gene
The subunit S5a is a key component for the recruitment of ubiquitinated substrates to the 26S proteasome. We previously found that the ectopic expression of ubiquitin‐interacting motifs of S5a (S5a‐UIMs) accumulated the ubiquitinated proteins in vivo and induced the A549 lung cancer cell death but not non‐cancer BEAS‐2B cell death. In this study, we further found that S5a‐UIMs induced cell cycle arrest in A549 cells and stabilized the p53, p21, and cyclins, but could not stabilize the unstable GFP, suggesting that it can be used as a selective upstream inhibitor of the proteasome pathway. In addition, S5a‐UIMs induced the cellular vacuolization in A549 cells, which may result from the perturbation of endocytosis. Ectopic expression of S5a‐UIMs also induced the ER stress in A549 cells, which was monitored by the increased expression of PDI, GRP78, GRP94, and caspase12. Taken together, our data suggest that S5a‐UIMs can induce the cellular vacuolization and ER stress, which may result in the A549 cell death.