Repression of protein translation and mTOR signaling by proteasome inhibitor in colon cancer cells

Journal Article · Fri Sep 04 04:00:00 EDT 2009 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2009.06.080· OSTI ID:22199780

Volta, Viviana ^[1]; Wu, Ya Chun; Li, Hai Tao ^[2]; Yu, Le ^[3]; Li, Zhi Jie ^[2]

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1. Molecular Histology and Cellular Growth Unit, DiBiT-San Raffaele Scientific Institute (Italy)
2. Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong (Hong Kong)
3. Institute of Digestive Diseases, Faculty of Medicine, The Chinese University of Hong Kong (Hong Kong)

Protein homeostasis relies on a balance between protein synthesis and protein degradation. The ubiquitin-proteasome system is a major catabolic pathway for protein degradation. In this respect, proteasome inhibition has been used therapeutically for the treatment of cancer. Whether inhibition of protein degradation by proteasome inhibitor can repress protein translation via a negative feedback mechanism, however, is unknown. In this study, proteasome inhibitor MG-132 lowered the proliferation of colon cancer cells HT-29 and SW1116. In this connection, MG-132 reduced the phosphorylation of mammalian target of rapamycin (mTOR) at Ser2448 and Ser2481 and the phosphorylation of its downstream targets 4E-BP1 and p70/p85 S6 kinases. Further analysis revealed that MG-132 inhibited protein translation as evidenced by the reductions of {sup 35}S-methionine incorporation and polysomes/80S ratio. Knockdown of raptor, a structural component of mTOR complex 1, mimicked the anti-proliferative effect of MG-132. To conclude, we demonstrate that the inhibition of protein degradation by proteasome inhibitor represses mTOR signaling and protein translation in colon cancer cells.

• OSTI ID: 22199780
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 386; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BIOSYNTHESIS
HOMEOSTASIS
INHIBITION
LARGE INTESTINE
METHIONINE
NEOPLASMS
PHOSPHORYLATION
PHOSPHOTRANSFERASES