Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Sci. Signal., 9 February 2010
Vol. 3, Issue 108, p. ra9
[DOI: 10.1126/scisignal.2000590]

RESEARCH ARTICLES

Editor's Summary

Inhibiting mTOR and Tumor Growth
The acetylase arrest-defective protein 1 (ARD1) has been implicated in mammalian cell proliferation and apoptosis, and the dysfunction of these processes contributes to cancer development. Kuo et al. searched an online database for a possible relationship between ARD1 and cancer and found that increased ARD1 mRNA abundance was associated with various measures of improved clinical outcome in patients with breast cancer, suggesting that ARD1 might act as a tumor suppressor. They uncovered ARD1 loss of heterozygosity (LOH) in primary breast cancer and several different cancer cell lines. Further analysis indicated that ARD1 acetylated—and thereby stabilized—tuberous sclerosis 2 (TSC2), part of a complex that inhibits signaling through the mammalian target of rapamycin (mTOR) pathway, a master regulator of cellular metabolism. ARD1-dependent inhibition of mTOR signaling decreased cell proliferation and increased autophagy, thereby suppressing tumor growth in nude mice. Moreover, ARD1 abundance correlated with that of TSC2 in various types of cancer. The authors thus propose that ARD1 suppressed development of multiple types of cancer through its stabilization of TSC2 and the consequent inhibition of mTOR signaling.

Citation: H.-P. Kuo, D.-F. Lee, C.-T. Chen, M. Liu, C.-K. Chou, H.-J. Lee, Y. Du, X. Xie, Y. Wei, W. Xia, Z. Weihua, J.-Y. Yang, C.-J. Yen, T.-H. Huang, M. Tan, G. Xing, Y. Zhao, C.-H. Lin, S.-F. Tsai, I. J. Fidler, M.-C. Hung, ARD1 Stabilization of TSC2 Suppresses Tumorigenesis Through the mTOR Signaling Pathway. Sci. Signal. 3, ra9 (2010).

Read the Full Text

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
N-{alpha}-Acetyltransferase 10 protein inhibits apoptosis through RelA/p65-regulated MCL1 expression.
H. Xu, B. Jiang, L. Meng, T. Ren, Y. Zeng, J. Wu, L. Qu, and C. Shou (2012)
Carcinogenesis 33, 1193-1202
   Abstract »    Full Text »    PDF »
Human Protein N-terminal Acetyltransferase hNaa50p (hNAT5/hSAN) Follows Ordered Sequential Catalytic Mechanism: COMBINED KINETIC AND NMR STUDY.
R. H. Evjenth, A. K. Brenner, P. R. Thompson, T. Arnesen, N. A. Froystein, and J. R. Lillehaug (2012)
J. Biol. Chem. 287, 10081-10088
   Abstract »    Full Text »    PDF »
Inactivation of androgen-induced regulator ARD1 inhibits androgen receptor acetylation and prostate tumorigenesis.
Z. Wang, Z. Wang, J. Guo, Y. Li, J. H. Bavarva, C. Qian, M. C. Brahimi-Horn, D. Tan, and W. Liu (2012)
PNAS 109, 3053-3058
   Abstract »    Full Text »    PDF »
mTOR Signaling, Function, Novel Inhibitors, and Therapeutic Targets.
R. Watanabe, L. Wei, and J. Huang (2011)
J. Nucl. Med. 52, 497-500
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882