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USP24‐inhibited c‐Myc expression represses lung cancer formation
Author(s) -
HUNG UA
Publication year - 2016
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.30.1_supplement.1108.1
Subject(s) - gene knockdown , pi3k/akt/mtor pathway , cancer research , rptor , ubiquitin , p70 s6 kinase 1 , ubiquitin ligase , biology , cell growth , transcription factor , microbiology and biotechnology , signal transduction , chemistry , apoptosis , gene , biochemistry
Lung cancer is a malignant lung cancer characterized by high incidence and motility. c‐Myc is a transcription factor that plays an important role in oncogenic activation to influence cellular metabolism and proliferation. Ubiquitin‐specific peptidase 24 (USP24) is one of the member of USPs family to regulate protein ubiquitination. However, it is lack of evidence to uncover the role of USP24 in cancer formation. In this study, we found that cell proliferation was significantly increased by USP24 knockdown in A549 cells as accompanied by the increase of c‐Myc protein. In particular, the RNA level and protein stability of c‐Myc were not affected by USP24 knockdown, suggesting that USP24 affects c‐Myc through regulating the translational pathway. Furthermore, c‐Myc participated in USP24‐knocked down‐induced proliferation, not migration. To further clarify the mechanism underlying the regulation of c‐Myc by USP24 knockdown. Herein rapamycin, the mTOR inhibitor, prevented c‐Myc up regulation caused by USP24 knockdown, suggesting that USP24 affect the protein level of c‐Myc by regulating mTOR‐mediated translation. We found that the downstream signaling of mTOR is activated by USP24 knockdown, including S6K and RPS6 phosphorylation. In addition, USP24 knockdown induced the binding of activated RPS6 to 5′‐UTR of c‐Myc, indicating that USP24 regulates c‐Myc through mTOR‐mediated translation. Understanding the role of USP24 in regulating mTOR pathway will contribute to develop strategies to fight lung cancer.