2. Academic Validation
  3. ARD1 stabilization of TSC2 suppresses tumorigenesis through the mTOR signaling pathway

ARD1 stabilization of TSC2 suppresses tumorigenesis through the mTOR signaling pathway

  • Sci Signal. 2010 Feb 9;3(108):ra9. doi: 10.1126/scisignal.2000590.
Hsu-Ping Kuo 1,  Dung-Fang Lee,  Chun-Te Chen,  Mo Liu,  Chao-Kai Chou,  Hong-Jen Lee,  Yi Du,  Xiaoming Xie,  Yongkun Wei,  Weiya Xia,  Zhang Weihua,  Jer-Yen Yang,  Chia-Jui Yen,  Tzu-Hsuan Huang,  Minjia Tan,  Gang Xing,  Yingming Zhao,  Chien-Hsing Lin,  Shih-Feng Tsai,  Isaiah J Fidler,  Mien-Chie Hung
Affiliations

Affiliation

  • 1 1Department of Molecular and Cellular Oncology, Unit 108, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
PMID: 20145209 DOI: 10.1126/scisignal.2000590
Abstract

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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