Reactome | TBC1D7 binds the TSC1-TSC2 complex

TBC1D7 binds the TSC1-TSC2 complex

Stable Identifier

R-HSA-8854302

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol

Synonyms

TBC1D7 binds TSC1-TSC2 complex

ReviewStatus

5/5

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TBC1D7 (TBC1 domain family, member 7) is a TBC (Tre-2/Bub2/Cdc16) 1 domain protein. Though TBC domain not only acts as a putative GTPase-activating protein (GAP) for small GTPases like Rab, it also have important role in cell cycle regulation and/or oncogenesis. The tuberous sclerosis complex (TSC) tumor suppressors form the TSC1-TSC2 complex that senses specific cellular conditions to control rapamycin (mTOR) complex 1 (mTORC1) signalling. TBC1D7 stably binds to TSC1 to form the third core subunit of TSC1-TSC2 complex. The TSC1-TSC2-TBC1D7 interaction helps stabilise these three proteins in the Rhebulator complex (Nakashima et al. 2007, Dibble et al. 2012). This TSC1-TSC2 complex acts as a GAP for the small G-protein RHEB, accelerating its conversion from its active GTP-bound state to its inactive GDP-form (Huang & Manning 2008). The active RHEB is required for activation of the mTORC1, a key promoter of cell growth. In poor growth conditions, the TSC1-TSC2 complex is activated to down-regulate TORC1 activity, whereas in response to growth factors, the TSC1-TSC2 complex is inactivated to allow RHEB-GTP-dependent stimulation of growth.

Literature References

PubMed ID	Title	Journal	Year
18466115	The TSC1-TSC2 complex: a molecular switchboard controlling cell growth Manning, BD, Huang, J	Biochem J	2008
22795129	TBC1D7 is a third subunit of the TSC1-TSC2 complex upstream of mTORC1 Murphy, LO, Elis, W, Manning, BD, Finan, PM, Klekota, J, Qin, W, Menon, S, Dibble, CC, Kwiatkowski, DJ, Asara, JM	Mol. Cell	2012
17658474	Identification of TBC7 having TBC domain as a novel binding protein to TSC1-TSC2 complex Miyamoto, T, Nakashima, A, Eguchi, S, Kikkawa, U, Yoshino, K, Yonezawa, K, Oshiro, N	Biochem. Biophys. Res. Commun.	2007
20095038	Activation of an oncogenic TBC1D7 (TBC1 domain family, member 7) protein in pulmonary carcinogenesis Daigo, Y, Nakamura, Y, Tsuchiya, E, Koinuma, J, Kondo, S, Sato, N, Ito, T	Genes Chromosomes Cancer	2010