期刊
SCIENCE SIGNALING
卷 3, 期 108, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scisignal.2000590
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资金
- NCI NIH HHS [P01 CA099031-01, P50 CA83639, R01 CA109311, P30 CA016672, P30 CA016672-34S5, CCSG CA16672, CA16672, P50 CA116199-050005, P50 CA083639-100009, R01 CA109311-06, P50 CA083639, P50 CA116199, P01 CA099031] Funding Source: Medline
Mammalian target of rapamycin (mTOR) regulates various cellular functions, including tumorigenesis, and is inhibited by the tuberous sclerosis 1 (TSC1)-TSC2 complex. Here, we demonstrate that arrest-defective protein 1 (ARD1) physically interacts with, acetylates, and stabilizes TSC2, thereby repressing mTOR activity. The inhibition of mTOR by ARD1 inhibits cell proliferation and increases autophagy, thereby inhibiting tumorigenicity. Correlation between ARD1 and TSC2 abundance was apparent in multiple tumor types. Moreover, evaluation of loss of heterozygosity at Xq28 revealed allelic loss in 31% of tested breast cancer cell lines and tumor samples. Together, our findings suggest that ARD1 functions as an inhibitor of the mTOR pathway and that dysregulation of the ARD1-TSC2-mTOR axis may contribute to cancer development.
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