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Tuberin

Definition:

In complex with TSC1, this tumor suppressor inhibits the nutrient-mediated or growth factor-stimulated phosphorylation of S6K1 and EIF4EBP1 by negatively regulating mTORC1 signaling. Acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1. May also play a role in microtubule-mediated protein transport (By similarity). Also stimulates the intrinsic GTPase activity of the Ras-related proteins RAP1A and RAB5 (By similarity).

References:

[1]. Jae Seok Lim, et al. Somatic Mutations in TSC1 and TSC2 Cause Focal Cortical Dysplasia. Am J Hum Genet. 2017 Mar 2;100(3):454-472. [Content Brief]

[2]. Yong Li, et al. Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity. Mol Cell Biol. 2004 Sep;24(18):7965-75. [Content Brief]

[3]. Eunus S Ali, et al. The mTORC1-SLC4A7 axis stimulates bicarbonate import to enhance de novo nucleotide synthesis. Mol Cell. 2022 Sep 1;82(17):3284-3298.e7. [Content Brief]

[4]. Andrew R Tee, et al. Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling. Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13571-6. [Content Brief]

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