EGF-mediated inhibition of ubiquitin-specific peptidase 24 expression has a crucial role in tumorigenesis

Shao-An Wang, Y. C. Wang, Y. P. Chuang, Yi Hsien Huang, W. C. Su, W. C. Chang, J. J. Hung

Research output: Contribution to journalArticle

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Abstract

In this study, several cancer-related proteins (Bax, p300, E2F4 and securin) have been proven to be substrates of ubiquitin-specific peptidase 24 (USP24), and relevance has been shown between USP24 and its substrates in samples from clinical lung cancer patients. Silencing USP24 increases the cancer formation by inhibiting cellular apoptosis and increasing cellular proliferation. Epidermal growth factor (EGF) treatment, and the Kras G12D and EGFR L858R mutations decrease USP24 protein stability via EGF-or CDK1-mediated phosphorylation at Ser1616, Ser2047 and Ser2604. Knockdown of USP24 decreases Bax and p300 levels, and reduces Ku70 acetylation, thereby preventing cancer cell apoptosis. In addition, knockdown of USP24 increases cell cycle progression by enhancing the G1-S transition and metaphase-anaphase transition. The molecular mechanism involves a decrease in the USP24 level, which reduces the expression of E2F4 and its partner TFDP1, and thus increases the G1/S transition. In conclusion, the USP24 level was decreased during the early stage of cancer and the mitotic stage of the cell cycle to regulate its substrates p300, Bax, E2F4 and securin, resulting in decreased cell apoptosis and increased cell cycle progression and, thus, cancer formation.

Original languageEnglish
Pages (from-to)2930-2945
Number of pages16
JournalOncogene
Volume36
Issue number21
DOIs
Publication statusPublished - May 25 2017

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Ubiquitin
Epidermal Growth Factor
Carcinogenesis
Peptide Hydrolases
Securin
Cell Cycle
Neoplasms
Apoptosis
bcl-2-Associated X Protein
Anaphase
Protein Stability
Metaphase
Acetylation
Lung Neoplasms
Phosphorylation
Cell Proliferation
Mutation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

EGF-mediated inhibition of ubiquitin-specific peptidase 24 expression has a crucial role in tumorigenesis. / Wang, Shao-An; Wang, Y. C.; Chuang, Y. P.; Huang, Yi Hsien; Su, W. C.; Chang, W. C.; Hung, J. J.

In: Oncogene, Vol. 36, No. 21, 25.05.2017, p. 2930-2945.

Research output: Contribution to journalArticle

Wang, Shao-An ; Wang, Y. C. ; Chuang, Y. P. ; Huang, Yi Hsien ; Su, W. C. ; Chang, W. C. ; Hung, J. J. / EGF-mediated inhibition of ubiquitin-specific peptidase 24 expression has a crucial role in tumorigenesis. In: Oncogene. 2017 ; Vol. 36, No. 21. pp. 2930-2945.
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