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J. Biol. Chem., Vol. 278, Issue 35, 32493-32496, August 29, 2003
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ACCELERATED PUBLICATIONS
¶
From the
Department of Biochemistry and Molecular
Biology, Indiana University School of Medicine and Walther Cancer Institute,
Indianapolis, Indiana 46202 and ||Department of
Cell and Cancer Biology, NCI, National Institutes of Health, Rockville,
Maryland 20850
Recently the tuberous sclerosis complex 2 (TSC2) tumor suppressor gene product has been identified as a negative regulator of protein synthesis upstream of the mTOR and ribosomal S6 kinases. Because of the homology of TSC2 with GTPase-activating proteins for Rap1, we examined whether a Ras/Rap-related GTPase might be involved in this process. TSC2 was found to bind to Rheb-GTP in vitro and to reduce Rheb GTP levels in vivo. Over-expression of Rheb but not Rap1 promoted the activation of S6 kinase in a rapamycin-dependent manner, suggesting that Rheb acts upstream of mTOR. The ability of Rheb to induce S6 phosphorylation was also inhibited by a farnesyl transferase inhibitor, suggesting that Rheb may be responsible for the Ras-independent anti-neoplastic properties of this drug.
Received for publication, May 29, 2003 , and in revised form, June 26, 2003.
* This work was supported by American Cancer Society Grant 00-125-01-TBE, an Indiana University Cancer Center Pilot Project grant, and an Indiana University Biomedical Research grant (to L. A. Q.) and a National Centers of Excellence in Women's Health grant (to A. F. C.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
¶ Supported by Training Grant T32-H07774 from NHLBI, National Institutes of Health.
To whom correspondence should be addressed: Dept. of Biochemistry and
Molecular Biology, Indiana University School of Medicine, 35 Barnhill Dr.,
MS-4053, Indianapolis, IN 46202-5122. Tel.: 317-278-3319; Fax: 317-274-4686;
E-mail:
acastro{at}iupui.edu.
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|
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|
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|
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|
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|
|
 |
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|
|
|
|
|
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