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phosphosite cbn pc11 biopax bel_lc signor biogrid tas lincs_drug hprd trrust | geneways tees isi trips rlimsp medscan sparser reach
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TSC2 affects TSC1
7 16 3 37 23 | 3 586 1693
7 15 2 37 12 | 3 444 1678
sparser
"Hamartin and tuberin form a heterodimer (TSC1/2) that is a central regulator of the mechanistic Target of Rapamycin Complex 1 (mTORC1)."
sparser
"Hamartin and tuberin associate in viva and patients with alterations in either gene show identi- cal symptoms [50’,51]."
hprd
No evidence text available
reach
"Signaling pathways, comprised of a number of oncogenes and tumor suppressors, converge on the TSC1 and TSC2 complex to properly regulate Rheb and mTORC1."
reach
"XREF_BIBR Accumulation of the TSC1 and TSC2 complex is achieved through competitive inhibition of complex formations between 14-3-3 and TSC2 by DNA-damage-inducible transcript 4 (DDIT4 or REDD1)."
reach
"Studies in human cells have shown that the TSC1 and TSC2 complex serves to inhibit TORC1 in the absence of pro growth hormones and/or the presence of AMPK activity, while we show that Kog1-body formation serves to inhibit TORC1 in the absence of glucose and the presence of AMPK activity."
reach
"The mechanism by which mTORC1 is regulated by tumor suppressor complex TSC1 and TSC2, LKB1 and PTEN signaling led to a growing appreciation that mTORC1 mediates three major inputs from growth factors, amino acids and ATP, and is a master regulator of cell growth and metabolism."
reach
"The TSC1 and TSC2 complex promotes stabilization of Rheb-GDP, and consequent inhibition of mTOR activity."
reach
"As such, the TSC1 and TSC2 complex senses many diverse extracellular signals to properly modulate mTORC1 activity."
reach
"TSC2 and TSC1 can form a dimer and inhibit the GTPase activity of Rheb, a critical activator of mTOR signaling XREF_BIBR."
1 | 21
sparser
"Indeed, the FIP200 N1-859 fragment, which can interact with the TSC1TSC2 complex ( xref A), showed similar activity as the full-length FIP200 in the inhibition of cell cycle progression as measured by BrdU incorporation (not depicted)."
sparser
"Similar studies indicated that the N1-859 segment of FIP200, but not the N1-638 segment, which does not bind to TSC1TSC2, also increased the average cell size of the transfected 293T cells ( xref )."
sparser
"FIP200 interaction with the TSC1TSC2 complex is not involved in FIP200 regulation of cell cycle progression."
sparser
"Together, these data suggest that interaction between FIP200 and the TSC1TSC2 complex is not involved in FIP200-mediated cell cycle progression."
sparser
"We found that association of FIP200 or its segments N1-859 and N1-638 with the TSC1TSC2 complex correlated with their ability to increase cell size, up-regulate S6K phosphorylation, and decrease TSC1–TSC complex formation."
sparser
"Association of FIP200 with the TSC1TSC2 complex."
sparser
"Together, these data suggest that FIP200 interaction with the TSC1TSC2 complex is not required for FIP200 regulation of cell cycle progression."
sparser
"Consistent with these transfection studies, we could also detect the interaction of endogenous FIP200 with the endogenous TSC1TSC2 complex in 293T cells ( xref E)."
sparser
"These results suggest that FIP200 interaction with the TSC1TSC2 complex might not be required for FIP200 regulation of cell cycle progression."
sparser
"Therefore our identification of the interaction between FIP200 and the TSC1TSC2 complex raises the interesting possibility that FIP200 may regulate cell size through interaction with the TSC1TSC2 complex."
1 | 12 8
reach
"The TSC1, TSC2, and TBC1D7 complex is the critical negative regulator of mTORC1 signalling with respect to most of its upstream regulators, such as growth factors, insulin and energy levels [XREF_BIBR]."
reach
"Complete loss of either TSC1 or TSC2 inactivates the TSC1, TSC2, and TBC1D7 complex leading to constitutive high-level activation of mTORC1 in TSC tumors."
reach
"Hence, exogenous expression of TSC1, as effected here by infection with a gene therapy vector can serve to rescue normal levels of the TSC1, TSC2, and TBC1D7 complex."
sparser
"The TSC complex, formed by the subunits TSC1, TSC2, and TBC1D7, is responsible for relaying most growth factor signaling pathways to mTORC1 (Ben‐Sahra & Manning, xref )."
sparser
"TSC1, TSC2, and TBC1D7 form a heteromeric complex that can bind to and stimulate the GTPase Ras homolog enriched in brain Rheb ( xref ; xref ; xref ; xref ) (for reviews see ( xref ; xref ) ( xref )."
sparser
"The interaction of TBC7 with the TSC1TSC2 complex was, however, not altered by the growth factor stimuli such as insulin, epidermal growth factor, and serum (data not shown)."
reach
"Our work gives more detailed insight into the structural and functional relationships between TSC1 and TBC1D7, and provides useful information for further studies aimed at unravelling the molecular structure of the TSC1, TSC2, and TBC1D7 complex."
reach
"The TSC1, TSC2, and TBC1D7 complex is an important negative regulator of the mechanistic target of rapamycin complex 1 that controls cell growth in response to environmental cues."
sparser
"TSC2 forms a complex with TSC1 and TBC1 domain family member 7 (TSC complex) and acts as a negative regulator of mTORC1 signaling xref , xref , xref ."
sparser
"Additional immunoprecipitations with antibodies that only recognize TSC2 phosphorylated by Akt on either S939 or T1462, confirmed that TSC1 and TBC1D7 readily associate with phosphorylated TSC2 and remain stably bound even after an hour of insulin stimulation ( xref )."
TSC1 binds TSC2 and MTOR. 10 / 10
| 10
sparser
"TSC1 and TSC2 gene products—hamartin and tuberin, respectively—are components of a complex that negatively regulates mTOR signaling and, correspondingly, inactivation of TSC1 or TSC2 is associated wit[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"Here we explored the hypothesis that mutations in MTOR , TSC1 or TSC2 are associated with response to rapalog therapy."
sparser
"For example, mutations in MTOR, TSC1 , or TSC2 were associated with response to mTOR inhibitors, 21% in responders versus 11% in non-responders ( xref )."
sparser
"Interaction of hamartin with tuberin forms a heterodimer that inhibits signaling by the mammalian target of rapamycin to its downstream targets: eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase 1 (S6K1)."
sparser
"Mutations of either tuberous sclerosis 1 (TSC1) or TSC2 are associated with aberrant activation of mammalian target of rapamycin (mTOR) pathway, which increases the risk of RCC ( xref , xref )."
sparser
"Tuberous sclerosis (TSC) is a monogenic disease resulting from defects of the TSC1 or TSC2 genes, which encode the proteins forming hamartin-tuberin tumor suppressor complex, the mammalian target of rapamycin complex (mTOR)."
sparser
"This is achieved via directly phosphorylation of Ser 1345 and Thr 1227 on the tumour suppressor protein tuberous sclerosis 2 (TSC2), which forms an mTOR complex 1 (mTORC1)-inhibitory complex with TSC1 [ xref ]."
sparser
"The genes code for the proteins hamartin (TSC1) and tuberin (TSC2) which form a complex that regulates the mTOR cell signalling pathway, responsible for important aspects of cell growth and differentiation [ xref ]."
sparser
"These results suggest that the identified TSC1 and TSC2 mutations are closely associated with both aberrant mTOR activation and dysregulation of neuronal growth in individuals with FCDII."
sparser
"In addition, TSC1 and TSC2 , which form a complex that negatively regulates mTOR activity, demonstrate decreased mRNA and protein levels in GBMs compared to grade II tumors and non-tumor brain."
TSC binds TSC1 and TSC2. 7 / 7
| 7
sparser
"In mouse models of TSC, loss of Tsc1 or Tsc2 is associated with abnormal neuronal connectivity – specifically neuronal polarity, axon formation and guidance [ xref – xref ]."
sparser
"Activated AKT inhibits the formation of the tuberous sclerosis proteins TSC1 and TSC2, thus allowing activation of MTOR."
sparser
"The two genes associated with TSC, TSC1 and TSC2 , were discovered by linkage analysis of large TSC families conducted by multinational consortia in 1997 and 1993, respectively."
sparser
"TSC is associated with mutations in 2 genes, TSC1 and TSC2, which encode hamartin and tuberin, respectively."
sparser
"TSC gene products TSC1 and TSC2 form a functional complex and inhibit cell growth."
sparser
"The overactivated mammalian target of rapamycin (mTOR) complex 1 (mTORC1) in TSC is associated with loss of function mutation in TSC1 and TSC2 genes ( xref , xref )."
sparser
"Two tumor suppressor genes, TSC1 and TSC2 , are associated with the development of TSC, and mutations in either gene are responsible for both the familial and sporadic forms of TSC ( Young and Pove[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
MTORC2 binds TSC1 and TSC2. 5 / 5
| 5
sparser
"The N-terminal region of TSC2 and C-terminal region of Rictor mediate the interaction between the TSC1-TSC2 complex and mTORC2."
sparser
"Most surprising was the finding that the TSC1-TSC2 complex can physically associate with components of mTORC2, but not those unique to mTORC1."
sparser
"In a previous study, we found that the TSC1-TSC2 complex can physically associate with mTORC2, but not mTORC1, and that the mTORC2 associated with the TSC1-TSC2 complex was catalytically active ( xref )."
sparser
"To avoid co-purification of endogenous mTORC2, we washed the immunoprecipitates with a high salt wash buffer found previously to disrupt binding of mTORC2 to the TSC1-TSC2 complex ( xref )."
sparser
"Finally, we find that the TSC1-TSC2 complex can physically associate with mTORC2 but not mTORC1."
TSC1 binds TSC1, TSC2, and TSC2. 4 / 4
| 4
sparser
"It is also possible that TSC1 facilitates the formation of TSC1-TSC2 complexes containing multiple TSC1 and TSC2 subunits."
sparser
"Therefore, it is unlikely that the detected TSC1TSC1 interactions are a consequence of the formation of TSC1TSC2 complexes containing multiple TSC1 and TSC2 subunits."
sparser
"TSC1 and TSC2 interact to form large complexes containing multiple TSC1 and TSC2 subunits."
sparser
"Hamartin and tuberin, the TSC1 and TSC2 gene products, interact and the tuberin-hamartin complex inhibits cell growth by antagonising signal transduction to downstream effectors of the mammalian target of rapamycin (mTOR) through the small GTPase rheb."
TSC1 binds TSC2 and TR3. 3 / 3
| 3
sparser
"The reciprocal precipitation also demonstrated that TR3 was associated with TSC1 and TSC2 (Supporting Information xref )."
sparser
"TSC1 and TSC2 both bound to the ligand-binding domain (LBD) of TR3 (Supporting Information xref )."
sparser
"TR3 bound to TSC2-TSC1 dimers and induced TSC2 ubiquitination and degradation, which led to the activation of mTORC1 but not mTORC2."
MTORC1 binds TSC1 and TSC2. 3 / 3
| 3
sparser
"While in our experiments relatively acute mTORC1 activation (< 24 hrs) did not alter postsynaptic function directly, there is evidence to suggest that longer, chronic hyperactivation of neuronal mTORC1, via knockdown of TSC1 or TSC2, is associated with morphological and functional changes in the postsynaptic compartment ( xref ; xref )."
sparser
"In the unstimulated condition, TSC1 forms a complex with TSC2, inhibiting mTORC1 [ xref , xref , xref – xref ]."
sparser
"Likewise, inactivating mutations in the TSC1 or TSC2 genes cause hamartoma syndromes associated with elevated mTORC1 activity ( xref , xref )."
P14_3_3 binds TSC1 and TSC2. 3 / 3
| 3
sparser
"The binding of the 14-3-3 protein to the TSC1-TSC2 complex prevents an inhibition of S6 kinase and the non-phosphorylation of 4E binding protein 1, i.e., it causes a weakening of the PI3K/PKB/TOR pathway signaling [ xref ]."
sparser
"Detection of a ternary complex of tuberin, hamartin and 14-3-3 suggests that the tuberin-14-3-3 interaction is compatible with tuberin-hamartin binding and that 14-3-3 proteins interact with the tuberin-hamartin complex [ xref , xref ]."
sparser
"We suggest that 14-3-3 proteins interact with the TSC1-TSC2 complex and negatively regulate the function of the TSC proteins."
TSC1 binds TSC2, PEX19, and PEX5. 3 / 3
| 3
sparser
"TSC1 and TSC2 bind peroxins PEX19 and PEX5."
sparser
"We found TSC1 and TSC2 bound to PEX19 and PEX5, respectively, and an ARL sequence required for PEX5 binding and localization to peroxisomal membranes was identified."
sparser
"TSC1 and TSC2 were bound by PEX19 and PEX5, respectively, and peroxisome-localized TSC functioned as a Rheb GAP to suppress mTORC1 and induce autophagy."
AKT binds TSC1 and TSC2. 2 / 2
| 2
sparser
"AKT associates with TSC1-TSC2 complexes, promoting phosphorylation of TSC2, and increases degradation of TSC1-TSC2 complexes [ xref ]."
sparser
"Inoki et al. observed a weakened interaction between Akt-phosphorylated TSC2 and TSC1 in mammalian cells, which lead to ubiquitin-mediated degradation of TSC2 ( xref )."
sparser
"This disorder is caused by mutations in TSC1 or TSC2 that encode tumour suppressor proteins which form the complex TSC1TSC2 that regulate protein synthesis in a wide range of mammalian cell types, including neurons xref ."
sparser
"TSC2 protein forms a heterodimeric tumour suppressor complex with TSC1, which is at the crossroads of many different signalling pathways, and serves as a nexus for integrating extracellular growth factor signalling and nutritional availability [ xref , xref ]."
AMPK binds TSC1 and TSC2. 2 / 2
| 2
sparser
"Co-immunoprecipitation and gel filtration analyses revealed an interaction between Sesn2 and AMPKα, suggesting that Sestrins are engaged in formation of a large protein complex containing AMPK and TSC1:TSC2."
sparser
"Sestrin 1 and 2 have been shown to interact with AMPK, TSC1, and TSC2 to inhibit mTOR signaling in response to genotoxic stress xref ."
RHEB binds TSC1 and TSC2. 2 / 2
| 2
sparser
"TSC2 forms a complex with TSC1 to promote GTP hydrolysis by the small GTPase Rheb."
sparser
"Growth factor signals and energy status are transmitted to mTOR C1 via TSC a complex of TSC1 and TSC2 proteins, which bind to Rheb and inhibit mTOR C1 activation."
TSC1 binds TSC2 and TOR. 2 / 2
| 2
sparser
"We show that Tsc1 and Tsc2 can physically associate with TOR and function upstream of TOR genetically."
sparser
"One possibility is that TOR and TSC1-TSC2 complexes associate with detergent-containing micelles."
TSC1 binds TSC2 and toxB. 2 / 2
| 2
sparser
"P. K. xref showed that two linked recessive genes on chromosome arm 3BL conferred resistance to race 3 (produces Ptr ToxC) and race 5 (produces Ptr ToxB) isolates in tetraploid wheat, indicating that the Tsc1 -Ptr ToxC and Tsc2 -Ptr ToxB interactions were not involved."
sparser
"The Tsn1 -Ptr ToxA, Tsc2 -Ptr ToxB, and Tsc1 -Ptr ToxC interactions have all been shown to play significant roles in the development of tan spot in common (hexaploid) wheat ( T. aestivum L. ssp. aestivum , 2 n = 6 x = 42, AABBDD genomes) ( xref ; xref )."
GAP binds TSC1 and TSC2. 2 / 2
| 2
sparser
"This is accomplished by AKT-1 phosphorylation and inactivation of TSC2 [ xref - xref ], which forms a TSC1TSC2 protein complex that is a GAP for the RHEB G-protein."
sparser
"The C-terminal domain of TSC2 contains a small region of homology with GTPase-activating proteins (GAPs), and TSC1 and TSC2 interact to form a complex that acts as a GAP for the small G-protein RHEB, accelerating the conversion of RHEB from its active GTP-bound state to its inactive GDP-bound form xref ."
TSC1 binds TSC2 and SESN2. 2 / 2
| 2
sparser
"None of these proteins was precipitated by the Flag antibody if they were coexpressed with GFP instead of Sesn2F. Reciprocal immunoprecipitation experiments confirmed the interaction of Sesn2 with TSC[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"None of these proteins was precipitated by the Flag antibody if they were co-expressed with GFP instead of Sesn2F. Reciprocal immunoprecipitation experiments confirmed the interaction of Sesn2 with TSC1, TSC2 and AMPKα2 ( xref )."
sparser
"To determine whether the Sestrins can interact with TSC1, TSC2 or AMPK, we expressed TSC1-Myc, TSC2-HA and AMPKα2-Myc together with Sesn2F in HEK293 cells."
sparser
"Sestrins interact with TSC1, TSC2 and AMPK."
GAP binds RHEB, TSC1, and TSC2. 2 / 2
| 2
sparser
"TBC1D7 knockdown decreases the association of TSC1 and TSC2 leading to decreased Rheb-GAP activity, without effects on the localization of TSC2 to the lysosome."
sparser
"TBC1D7 knockdown using siRNA decreased the association of TSC1 and TSC2 resulting in the decrease of Rheb-GAP activity."
AMPK binds TSC1, TSC2, and MTOR. 2 / 2
| 2
sparser
"The complex of hamartin (TSC1) and tuberin (TSC2) interact with AMPK and mTOR, and mutations in TSC1 or TSC2 lead to uncontrolled cell growth. xref TSC is associated with characteristic neoplasms such as neurofibromas in the skin, angiomyolipoma in the kidney and LAM in the lung."
sparser
"Sestrins inhibit mTORC1 activity by interacting with mTOR pathway suppressors AMPK, TSC1, and TSC2 [ xref ]."
GAP binds mTORC1, RHEB, TSC1, and TSC2. 2 / 2
| 2
sparser
"Most of these signals exert their effect on mTORC1 by modulating the activity of the tuberous sclerosis complex proteins, TSC1 and TSC2, which form a heterodimer that functions as a GTPase activating [MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"Most of these signals exert their effect on mTORC1 by modulating the activity of the tuberous sclerosis complex proteins, TSC1 and TSC2, which form a heterodimer that functions as a GTPase activating protein (GAP) to inhibit the activity of the small GTPase Rheb ( xref )."
Phosphorylated TSC1 binds TSC2. 1 / 1
| 1
reach
"The phosphorylated TSC1 and TSC2 complex inactivates the Rheb GTP component needed for mTOR signaling."
TSC1 binds mutated TSC2. 1 / 1
| 1
reach
"Loss-of-function mutations of the tuberin and hamartin complex impair GTPase activity, leading to constitutive activation of these proteins."
TSC1 bound to TSC2 binds TSC2. 1 / 1
1 |
signor
"TSC1 and TSC2 proteins form a physical and functional complex in vivo. Here, we show that TSC1-TSC2 inhibits the p70 ribosomal protein S6 kinase 1 (an activator of translation) and activates the eukaryotic initiation factor 4E binding protein 1 (4E-BP1, an inhibitor of translational initiation). These functions of TSC1-TSC2 are mediated by inhibition of the mammalian target of rapamycin (mTOR)."
Mutated TSC1 binds TSC2. 1 / 1
| 1
reach
"Inactivating mutations of the TSC1 and TSC2 complex (TSC1/2) cause tuberous sclerosis (TSC), a hereditary syndrome with neurological symptoms and benign hamartoma tumours in the brain."
TSC1 binds TSC2 and PAM. 1 / 1
| 1
sparser
"Our studies show that Pam interacts with the TSC1-TSC2 complex, and regulates mTORC1 signaling [ xref , xref , xref ]."
VEGF binds TSC1 and TSC2. 1 / 1
| 1
sparser
"Loss of the TSC1 or TSC2 gene has been associated with increased production of vascular endothelial growth factor (VEGF), and inhibitors of mTOR have been shown to have an inhibitory effect on production of VEGF, tumor growth, and angiogenesis, both in vitro and in vivo. xref , xref "
TSC1 binds TSC2 and 293T. 1 / 1
| 1
reach
"Consistent with these transfection studies, we could also detect the interaction of endogenous FIP200 with the endogenous TSC1 and TSC2 complex in 293T cells (XREF_FIG E)."
TSC1 binds TSC2 and SIRT1. 1 / 1
| 1
sparser
"Our results demonstrate that SIRT1 and mTOR signaling pathways are indeed interconnected in a way that promotes stress sensing pro-survival signals, where the regulation of mTOR is mediated potentially through an interaction of SIRT1 with the TSC1-TSC2 complex."
TSC1 binds TSC2 and proline. 1 / 1
| 1
reach
"Perhaps the most dramatic metabolic consequence of PI3K and Akt stimulation however, is downstream activation of the cell growth regulator mechanistic target of rapamycin complex 1 (mTORC1) upon Akt mediated phosphorylation of either of two mTORC1 inhibitors : tuberous sclerosis 2 (TSC2; part of the TSC1 and TSC2 complex) or proline rich Akt substrate 40 kDa (PRAS40)."
TSC1 binds TSC2 and casE. 1 / 1
| 1
sparser
"Results showed that TSC1 mutations in the tuberin interaction domain were significantly associated with lower intellectual outcomes (P<0.03), which was also the case for TSC2 protein-truncating and hamartin interaction domain mutations (both P<0.05)."
TSC1 binds TSC2 and YWHAQ. 1 / 1
1 |
hprd
No evidence text available
TGFB1 binds TSC1 and TSC2. 1 / 1
| 1
sparser
"Furthermore, we found that reduced expression of TSC1 and TSC2 caused by TGF-β1 is associated with the promoter methylation status of TSC1 and TSC2."
TSC1 binds TSC2 and TBC1 domain. 1 / 1
| 1
reach
"TSC2 forms a complex with TSC1 and TBC1 domain family member 7 (TSC complex) and acts as a negative regulator of mTORC1 signaling XREF_BIBR, XREF_BIBR, XREF_BIBR."
| 1
sparser
"Also it is suggested that TSC1 interacts with TSC2 to stabilize TSC2 by excluding HERC1 ubiquitin ligase from the TSC2 complex xref ."
TSC1 binds TSC2 and PTK2. 1 / 1
1 |
hprd
No evidence text available
TSC1 binds TSC2 and TRX1. 1 / 1
| 1
sparser
"We showed that pUL38 interacts with TSC1 and TSC2 in cells infected with wild-type cytomegalovirus."
TSC1 binds TSC2 and PAM. 1 / 1
1 |
hprd
No evidence text available
TSC1 binds TSC2 and CDKN1B. 1 / 1
| 1
sparser
"Whereas tuberin also binds p27 in TSC1-negative cells, hamartin does not bind p27 without tuberin."
TSC1 binds TSC2 and RHOA. 1 / 1
| 1
sparser
"Because TSC2 binds TSC1 ( xref , xref ; xref ) by the domain that overlaps the Rho-activating domain of TSC1 and potentially inhibits TSC1-dependent Rho activation, we investigated whether or not stress fiber disassembly involves TSC1."
TSC1 binds TSC2 and PKD1. 1 / 1
| 1
sparser
"Using mouse models, we showed a genetic interaction between Tsc1 and Tsc2 with Pkd1 and confirmed an mTOR-independent pathway of renal cystogenesis."
TSC1 binds TSC2 and FBXW5. 1 / 1
1 |
hprd
No evidence text available
TSC1 binds TSC2 and CTNNB1. 1 / 1
| 1
sparser
"Second, hamartin and tuberin interacts with components of the β-catenin destruction complex, thus regulate Wnt/β-catenin signaling xref ."
TSC1 binds TSC2 and PLK1. 1 / 1
1 |
hprd
No evidence text available
TSC1 binds TSC2 and YWHAZ. 1 / 1
| 1
sparser
"The interaction between tuberin and 14-3-3zeta was confirmed in vitro and by co-immunoprecipitation; multiple sites within tuberin for 14-3-3zeta binding were identified; and it was determined that 14-3-3zeta associated with the tuberin-hamartin complex."
TSC1 binds TSC2 and EGFR. 1 / 1
| 1
sparser
"We then wondered whether expression of hamartin, p-mTOR or p-TSC2 was associated with EGFR-mutations since approximately 20% of adenocarcinoma of the lung patients’ specimens reveal EGFR-mutations [ xref ]."
TP53 binds TSC1 and TSC2. 1 / 1
| 1
sparser
"Further application of full exome and genome sequencing will likely uncover additional evidence of genetic interactions between TP53 and both TSC1 and TSC2 in a variety of human cancers."
TSC1 binds TSC2 and PTEN. 1 / 1
| 1
sparser
"We further demonstrate that Akt/PKB associates with hamartin-tuberin complexes, promoting phosphorylation of tuberin and increased degradation of hamartin-tuberin complexes."
TSC1 binds TSC2 and DOCK7. 1 / 1
1 |
hprd
No evidence text available
TSC1 binds TSC2 and ARSD. 1 / 1
| 1
sparser
"ASD was not associated with TSC1 or TSC2 mutations ( P = 1.0)."
TSC1 binds TSC2 and catenin. 1 / 1
| 1
sparser
"It is interesting to note that the tumor suppressor complex formed by TSC1 and TSC2 interacts with the β -catenin degradation complex and thus modulates the action of Wnt signaling [ xref , xref ]."
TSC1 binds TSC2 and PIK3C3. 1 / 1
| 1
sparser
"Given that TSC1 is required for the stability of TSC2 [ xref ], we hypothesized that binding of VPS34 to TSC1 disengaged TSC1/TSC2 heterodimer, which may lead to degradation of TSC2."
TSC1 binds TSC2 and ATXN3. 1 / 1
| 1
sparser
"PEComas are related to the genetic alterations of tuberous sclerosis complex (TSC), an autosomal dominant genetic disease associated with losses of TSC1 (9q34) or TSC2 (16p13.3) genes, which seem to have a role in the regulation of the Rheb/mTOR/p70S6K pathway."
TSC1 binds TSC2 and Hsp90α. 1 / 1
| 1
sparser
"Surprisingly, direct interaction of Tsc2 and Hsp90α‐His 6 did not occur in vitro ; however, pre‐incubation of Hsp90α‐His 6 with Tsc1 facilitated the formation of Hsp90α:Tsc1:Tsc2 complex (Fig  xref F)."
HSP90 binds TSC1 and TSC2. 1 / 1
| 1
sparser
"To determine Tsc1 and Tsc2 interaction with these Hsp90 domains, we transiently transfected and expressed each domain with FLAG‐tag in HEK293 cells."
ERK binds TSC1 and TSC2. 1 / 1
| 1
sparser
"As a result, upon abrogation of basal levels of Erk activity, wild-type TSC2 binds TSC1 as strongly as TSC2 S664A/S540A , suggesting that the observed stronger interaction between TSC1 and the TSC2 S6[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
TSC1 binds TSC2 and RICTOR. 1 / 1
| 1
sparser
"However, when either mTOR or mSin1 were omitted, only Rictor bound to the TSC1-TSC2 complex, demonstrating that Rictor is sufficient for the association."
TSC1 binds TSC2 and D1. 1 / 1
| 1
reach
"It was suggested that TSC1 and TSC2 complex may regulate Cyclin D1 expression through canonical Wnt and beta-catenin signaling."
TSC1 binds TSC2 and CCND1. 1 / 1
1 |
hprd
No evidence text available
TSC1 binds TSC2 and PLK2. 1 / 1
| 1
sparser
"We have demonstrated that Plk2 interacts with both TSC1 (endogenous, CT-Plk2) and TSC2 (CT-Plk2) in various cell types."
| 1
sparser
"Previous work has also shown that Tsc1 and Tsc2 both interact with the co‐chaperone complex R2TP/Prefoldin‐like (R2TP/PFDL) complex (Cloutier et al , xref )."
RHEB binds TSC1, TSC2, and MTOR. 1 / 1
| 1
sparser
"Full-length TSC2 protein interacts with TSC1 to inhibit the activation of mTOR by Rheb."
TSC1 binds TSC2, MTOR, and cKO. 1 / 1
| 1
sparser
"The global follicle activation phenotype previously documented in Tsc1 or Tsc2 cKO females was associated with dramatic upregulation of the mTOR signaling pathway (demonstrable with the same immunohistochemical assays performed in our study) ( xref , xref ), yet Rheb conditional inactivation in oocytes did not have any observable effect on follicle maturation."
GST binds TSC1, TSC2, and TBC1D7. 1 / 1
| 1
sparser
"Furthermore, the pull-down analysis showed that both of TSC1 and TSC2 obtained from HEK293 cells bound to the bacterial GST-TBC7 in a dose-dependent manner, but not to the control protein (D)."
sparser
"Next, we co-transfected HeLa cells with different forms of myc-TSC1 with HA-TSC2 and treated with nocodazole."
GST binds TSC1, TSC2, and PLK2. 1 / 1
| 1
sparser
"Additionally, C-terminal Plk2-GST fusion protein bound both TSC1 and TSC2 proteins."
| 1
sparser
"Since in control experiments, Tsc1 and Tsc2 do not bind to Luciferase or GST, respectively (Figure 4) , the binding between Tsc1 and Tsc2 was unlikely due to nonspecific sticking."
TSC1 binds TSC2, PEX19, and Flag. 1 / 1
| 1
sparser
"While a very small amount of Flag-TSC2 was associated with the PEX19-TSC1 complex ( xref ), this association was abrogated with the TSC2-G294E mutant (a TSC1 binding-deficient mutant xref ), indicating the little TSC2 detected in this complex was likely associated with TSC1, rather than directly bound to PEX19 ( xref )."
TSC1 binds TSC2, MMP2, and PHEX. 1 / 1
| 1
sparser
"Here we show that TSC1 and TSC2 associate with PEX proteins and are localized to peroxisomal membranes, where they regulate mTORC1 signaling in response to ROS."
MTORC1 binds RHEB, TSC1, and TSC2. 1 / 1
| 1
sparser
"Loss-of-function TSC1 or TSC2 mutations are associated with increased Rheb-GTP levels and aberrant activation of mTORC1 in various TSC-associated hamartomas ( xref , xref )."
MTORC1 binds TSC1, TSC2, and NCAPD2. 1 / 1
| 1
sparser
"The finding of the association of mTORC1 with the bipartite complex TSC1 and TSC2 of tumor suppressor proteins provided a molecular link between mTOR and cancer (reviewed in REF xref )."
TSC1 binds TSC2, RB1CC1, and MEF. 1 / 1
| 1
sparser
"Together, these results demonstrate that FIP200 could associate with the TSC1TSC2 complex in mammalian cells such as 293T cells and MEFs."
TSC binds TSC1, TSC2, and MTOR. 1 / 1
| 1
sparser
"TSC is associated with mutations in TSC1 or TSC2, resulting in hyperactivation of mTOR complex 1 (mTORC1)."
TSC1 binds TSC2, GSK3B, and AXIN1. 1 / 1
1 |
hprd
No evidence text available
TSC binds TSC1, TSC2, and TBC1D7. 1 / 1
| 1
sparser
"This interaction is inhibited by the Rheb-GTPase activating protein (GAP) activity of the tuberous sclerosis protein complex (TSC) that is formed by the TSC1, TSC2 and TBC1D7 proteins [ xref ]."
AMPK binds TSC1, TSC2, and SESN2. 1 / 1
| 1
sparser
"To study whether a complex containing Sesn2, TSC1, TSC2 and AMPK can form under more physiological conditions, we immunoprecipitated lysates of MCF7-tet OFF Sesn2F or MCF7-tet OFF GFP cells with the Flag antibody."
TSC1 binds TSC2, STRADA, and PTEN. 1 / 1
| 1
sparser
"Among these, TSC1, TSC2, STRADα and PTEN are associated with epilepsy and autism in humans and animal models."
sparser
"The TSC1 and TSC2 proteins assemble into a complex that is stabilized by TBC1D7 through its direct interaction with the TSC1 coiled coil (CC) region."
AXIN binds Wnt, TSC1, TSC2, and CTNNB1. 1 / 1
| 1
sparser
"Both TSC1 and TSC2 are able to associate with Axin and β-catenin in the canonical Wnt pathway, and an absence of either TSC1 or TSC2 has shown to increase Wnt signaling ( Mak, Takemaru, Kenerson, Moon[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
| 1
sparser
"Likewise, we find increased binding of TSC2, TSC1 and TBC1D7 to the Rag GTPases in response to various stresses ( xref ), in agreement with relocalization of the entire TSC complex to lysosomes."
TSC1 binds TSC1, TSC2, TSC2, and ATXN3. 1 / 1
| 1
sparser
"TSC is an autosomal dominant disease that is associated with gene mutations of TSC1 or TSC2 , encoding hamartin and tuberin, respectively [ xref ]."
1 |
hprd
No evidence text available
TSC binds TSC1, TSC1, TSC2, and TSC2. 1 / 1
| 1
sparser
"Genetically, TSC is associated with mutations in TSC1 or TSC2 (located on 9q 34 and 16q13 respectively), leading to impaired production of the proteins hamartin and tuberin respectively."
AMPK binds TP53, TSC1, TSC2, and MTOR. 1 / 1
| 1
sparser
"The antioxidant response of p53 also inhibits the mTOR pathway via the Sestrins, which are induced by p53 and can interact with mTOR pathway suppressors AMPK, TSC1 and TSC2 [ xref ]."
sparser
"Tuberous sclerosis complex is exclusively associated with mutations in either the TSC1 or TSC2 tumour suppressor gene, which encodes the proteins hamartin and tuberin, respectively."
1 |
hprd
No evidence text available
TSC1 affects TSC2
7 16 3 37 23 | 3 586 1693
7 15 2 37 12 | 3 444 1678
sparser
"Hamartin and tuberin form a heterodimer (TSC1/2) that is a central regulator of the mechanistic Target of Rapamycin Complex 1 (mTORC1)."
sparser
"Hamartin and tuberin associate in viva and patients with alterations in either gene show identi- cal symptoms [50’,51]."
hprd
No evidence text available
reach
"Signaling pathways, comprised of a number of oncogenes and tumor suppressors, converge on the TSC1 and TSC2 complex to properly regulate Rheb and mTORC1."
reach
"XREF_BIBR Accumulation of the TSC1 and TSC2 complex is achieved through competitive inhibition of complex formations between 14-3-3 and TSC2 by DNA-damage-inducible transcript 4 (DDIT4 or REDD1)."
reach
"Studies in human cells have shown that the TSC1 and TSC2 complex serves to inhibit TORC1 in the absence of pro growth hormones and/or the presence of AMPK activity, while we show that Kog1-body formation serves to inhibit TORC1 in the absence of glucose and the presence of AMPK activity."
reach
"The mechanism by which mTORC1 is regulated by tumor suppressor complex TSC1 and TSC2, LKB1 and PTEN signaling led to a growing appreciation that mTORC1 mediates three major inputs from growth factors, amino acids and ATP, and is a master regulator of cell growth and metabolism."
reach
"The TSC1 and TSC2 complex promotes stabilization of Rheb-GDP, and consequent inhibition of mTOR activity."
reach
"As such, the TSC1 and TSC2 complex senses many diverse extracellular signals to properly modulate mTORC1 activity."
reach
"TSC2 and TSC1 can form a dimer and inhibit the GTPase activity of Rheb, a critical activator of mTOR signaling XREF_BIBR."
1 | 21
sparser
"Indeed, the FIP200 N1-859 fragment, which can interact with the TSC1TSC2 complex ( xref A), showed similar activity as the full-length FIP200 in the inhibition of cell cycle progression as measured by BrdU incorporation (not depicted)."
sparser
"Similar studies indicated that the N1-859 segment of FIP200, but not the N1-638 segment, which does not bind to TSC1TSC2, also increased the average cell size of the transfected 293T cells ( xref )."
sparser
"FIP200 interaction with the TSC1TSC2 complex is not involved in FIP200 regulation of cell cycle progression."
sparser
"Together, these data suggest that interaction between FIP200 and the TSC1TSC2 complex is not involved in FIP200-mediated cell cycle progression."
sparser
"We found that association of FIP200 or its segments N1-859 and N1-638 with the TSC1TSC2 complex correlated with their ability to increase cell size, up-regulate S6K phosphorylation, and decrease TSC1–TSC complex formation."
sparser
"Association of FIP200 with the TSC1TSC2 complex."
sparser
"Together, these data suggest that FIP200 interaction with the TSC1TSC2 complex is not required for FIP200 regulation of cell cycle progression."
sparser
"Consistent with these transfection studies, we could also detect the interaction of endogenous FIP200 with the endogenous TSC1TSC2 complex in 293T cells ( xref E)."
sparser
"These results suggest that FIP200 interaction with the TSC1TSC2 complex might not be required for FIP200 regulation of cell cycle progression."
sparser
"Therefore our identification of the interaction between FIP200 and the TSC1TSC2 complex raises the interesting possibility that FIP200 may regulate cell size through interaction with the TSC1TSC2 complex."
1 | 12 8
reach
"The TSC1, TSC2, and TBC1D7 complex is the critical negative regulator of mTORC1 signalling with respect to most of its upstream regulators, such as growth factors, insulin and energy levels [XREF_BIBR]."
reach
"Complete loss of either TSC1 or TSC2 inactivates the TSC1, TSC2, and TBC1D7 complex leading to constitutive high-level activation of mTORC1 in TSC tumors."
reach
"Hence, exogenous expression of TSC1, as effected here by infection with a gene therapy vector can serve to rescue normal levels of the TSC1, TSC2, and TBC1D7 complex."
sparser
"The TSC complex, formed by the subunits TSC1, TSC2, and TBC1D7, is responsible for relaying most growth factor signaling pathways to mTORC1 (Ben‐Sahra & Manning, xref )."
sparser
"TSC1, TSC2, and TBC1D7 form a heteromeric complex that can bind to and stimulate the GTPase Ras homolog enriched in brain Rheb ( xref ; xref ; xref ; xref ) (for reviews see ( xref ; xref ) ( xref )."
sparser
"The interaction of TBC7 with the TSC1TSC2 complex was, however, not altered by the growth factor stimuli such as insulin, epidermal growth factor, and serum (data not shown)."
reach
"Our work gives more detailed insight into the structural and functional relationships between TSC1 and TBC1D7, and provides useful information for further studies aimed at unravelling the molecular structure of the TSC1, TSC2, and TBC1D7 complex."
reach
"The TSC1, TSC2, and TBC1D7 complex is an important negative regulator of the mechanistic target of rapamycin complex 1 that controls cell growth in response to environmental cues."
sparser
"TSC2 forms a complex with TSC1 and TBC1 domain family member 7 (TSC complex) and acts as a negative regulator of mTORC1 signaling xref , xref , xref ."
sparser
"Additional immunoprecipitations with antibodies that only recognize TSC2 phosphorylated by Akt on either S939 or T1462, confirmed that TSC1 and TBC1D7 readily associate with phosphorylated TSC2 and remain stably bound even after an hour of insulin stimulation ( xref )."
TSC1 binds TSC2 and MTOR. 10 / 10
| 10
sparser
"TSC1 and TSC2 gene products—hamartin and tuberin, respectively—are components of a complex that negatively regulates mTOR signaling and, correspondingly, inactivation of TSC1 or TSC2 is associated wit[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"Here we explored the hypothesis that mutations in MTOR , TSC1 or TSC2 are associated with response to rapalog therapy."
sparser
"For example, mutations in MTOR, TSC1 , or TSC2 were associated with response to mTOR inhibitors, 21% in responders versus 11% in non-responders ( xref )."
sparser
"Interaction of hamartin with tuberin forms a heterodimer that inhibits signaling by the mammalian target of rapamycin to its downstream targets: eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase 1 (S6K1)."
sparser
"Mutations of either tuberous sclerosis 1 (TSC1) or TSC2 are associated with aberrant activation of mammalian target of rapamycin (mTOR) pathway, which increases the risk of RCC ( xref , xref )."
sparser
"Tuberous sclerosis (TSC) is a monogenic disease resulting from defects of the TSC1 or TSC2 genes, which encode the proteins forming hamartin-tuberin tumor suppressor complex, the mammalian target of rapamycin complex (mTOR)."
sparser
"This is achieved via directly phosphorylation of Ser 1345 and Thr 1227 on the tumour suppressor protein tuberous sclerosis 2 (TSC2), which forms an mTOR complex 1 (mTORC1)-inhibitory complex with TSC1 [ xref ]."
sparser
"The genes code for the proteins hamartin (TSC1) and tuberin (TSC2) which form a complex that regulates the mTOR cell signalling pathway, responsible for important aspects of cell growth and differentiation [ xref ]."
sparser
"These results suggest that the identified TSC1 and TSC2 mutations are closely associated with both aberrant mTOR activation and dysregulation of neuronal growth in individuals with FCDII."
sparser
"In addition, TSC1 and TSC2 , which form a complex that negatively regulates mTOR activity, demonstrate decreased mRNA and protein levels in GBMs compared to grade II tumors and non-tumor brain."
TSC binds TSC1 and TSC2. 7 / 7
| 7
sparser
"In mouse models of TSC, loss of Tsc1 or Tsc2 is associated with abnormal neuronal connectivity – specifically neuronal polarity, axon formation and guidance [ xref – xref ]."
sparser
"Activated AKT inhibits the formation of the tuberous sclerosis proteins TSC1 and TSC2, thus allowing activation of MTOR."
sparser
"The two genes associated with TSC, TSC1 and TSC2 , were discovered by linkage analysis of large TSC families conducted by multinational consortia in 1997 and 1993, respectively."
sparser
"TSC is associated with mutations in 2 genes, TSC1 and TSC2, which encode hamartin and tuberin, respectively."
sparser
"TSC gene products TSC1 and TSC2 form a functional complex and inhibit cell growth."
sparser
"The overactivated mammalian target of rapamycin (mTOR) complex 1 (mTORC1) in TSC is associated with loss of function mutation in TSC1 and TSC2 genes ( xref , xref )."
sparser
"Two tumor suppressor genes, TSC1 and TSC2 , are associated with the development of TSC, and mutations in either gene are responsible for both the familial and sporadic forms of TSC ( Young and Pove[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
MTORC2 binds TSC1 and TSC2. 5 / 5
| 5
sparser
"The N-terminal region of TSC2 and C-terminal region of Rictor mediate the interaction between the TSC1-TSC2 complex and mTORC2."
sparser
"Most surprising was the finding that the TSC1-TSC2 complex can physically associate with components of mTORC2, but not those unique to mTORC1."
sparser
"In a previous study, we found that the TSC1-TSC2 complex can physically associate with mTORC2, but not mTORC1, and that the mTORC2 associated with the TSC1-TSC2 complex was catalytically active ( xref )."
sparser
"To avoid co-purification of endogenous mTORC2, we washed the immunoprecipitates with a high salt wash buffer found previously to disrupt binding of mTORC2 to the TSC1-TSC2 complex ( xref )."
sparser
"Finally, we find that the TSC1-TSC2 complex can physically associate with mTORC2 but not mTORC1."
TSC1 binds TSC1, TSC2, and TSC2. 4 / 4
| 4
sparser
"It is also possible that TSC1 facilitates the formation of TSC1-TSC2 complexes containing multiple TSC1 and TSC2 subunits."
sparser
"Therefore, it is unlikely that the detected TSC1TSC1 interactions are a consequence of the formation of TSC1TSC2 complexes containing multiple TSC1 and TSC2 subunits."
sparser
"TSC1 and TSC2 interact to form large complexes containing multiple TSC1 and TSC2 subunits."
sparser
"Hamartin and tuberin, the TSC1 and TSC2 gene products, interact and the tuberin-hamartin complex inhibits cell growth by antagonising signal transduction to downstream effectors of the mammalian target of rapamycin (mTOR) through the small GTPase rheb."
TSC1 binds TSC2 and TR3. 3 / 3
| 3
sparser
"The reciprocal precipitation also demonstrated that TR3 was associated with TSC1 and TSC2 (Supporting Information xref )."
sparser
"TSC1 and TSC2 both bound to the ligand-binding domain (LBD) of TR3 (Supporting Information xref )."
sparser
"TR3 bound to TSC2-TSC1 dimers and induced TSC2 ubiquitination and degradation, which led to the activation of mTORC1 but not mTORC2."
MTORC1 binds TSC1 and TSC2. 3 / 3
| 3
sparser
"While in our experiments relatively acute mTORC1 activation (< 24 hrs) did not alter postsynaptic function directly, there is evidence to suggest that longer, chronic hyperactivation of neuronal mTORC1, via knockdown of TSC1 or TSC2, is associated with morphological and functional changes in the postsynaptic compartment ( xref ; xref )."
sparser
"In the unstimulated condition, TSC1 forms a complex with TSC2, inhibiting mTORC1 [ xref , xref , xref – xref ]."
sparser
"Likewise, inactivating mutations in the TSC1 or TSC2 genes cause hamartoma syndromes associated with elevated mTORC1 activity ( xref , xref )."
P14_3_3 binds TSC1 and TSC2. 3 / 3
| 3
sparser
"The binding of the 14-3-3 protein to the TSC1-TSC2 complex prevents an inhibition of S6 kinase and the non-phosphorylation of 4E binding protein 1, i.e., it causes a weakening of the PI3K/PKB/TOR pathway signaling [ xref ]."
sparser
"Detection of a ternary complex of tuberin, hamartin and 14-3-3 suggests that the tuberin-14-3-3 interaction is compatible with tuberin-hamartin binding and that 14-3-3 proteins interact with the tuberin-hamartin complex [ xref , xref ]."
sparser
"We suggest that 14-3-3 proteins interact with the TSC1-TSC2 complex and negatively regulate the function of the TSC proteins."
TSC1 binds TSC2, PEX19, and PEX5. 3 / 3
| 3
sparser
"TSC1 and TSC2 bind peroxins PEX19 and PEX5."
sparser
"We found TSC1 and TSC2 bound to PEX19 and PEX5, respectively, and an ARL sequence required for PEX5 binding and localization to peroxisomal membranes was identified."
sparser
"TSC1 and TSC2 were bound by PEX19 and PEX5, respectively, and peroxisome-localized TSC functioned as a Rheb GAP to suppress mTORC1 and induce autophagy."
AKT binds TSC1 and TSC2. 2 / 2
| 2
sparser
"AKT associates with TSC1-TSC2 complexes, promoting phosphorylation of TSC2, and increases degradation of TSC1-TSC2 complexes [ xref ]."
sparser
"Inoki et al. observed a weakened interaction between Akt-phosphorylated TSC2 and TSC1 in mammalian cells, which lead to ubiquitin-mediated degradation of TSC2 ( xref )."
sparser
"This disorder is caused by mutations in TSC1 or TSC2 that encode tumour suppressor proteins which form the complex TSC1TSC2 that regulate protein synthesis in a wide range of mammalian cell types, including neurons xref ."
sparser
"TSC2 protein forms a heterodimeric tumour suppressor complex with TSC1, which is at the crossroads of many different signalling pathways, and serves as a nexus for integrating extracellular growth factor signalling and nutritional availability [ xref , xref ]."
AMPK binds TSC1 and TSC2. 2 / 2
| 2
sparser
"Co-immunoprecipitation and gel filtration analyses revealed an interaction between Sesn2 and AMPKα, suggesting that Sestrins are engaged in formation of a large protein complex containing AMPK and TSC1:TSC2."
sparser
"Sestrin 1 and 2 have been shown to interact with AMPK, TSC1, and TSC2 to inhibit mTOR signaling in response to genotoxic stress xref ."
RHEB binds TSC1 and TSC2. 2 / 2
| 2
sparser
"TSC2 forms a complex with TSC1 to promote GTP hydrolysis by the small GTPase Rheb."
sparser
"Growth factor signals and energy status are transmitted to mTOR C1 via TSC a complex of TSC1 and TSC2 proteins, which bind to Rheb and inhibit mTOR C1 activation."
TSC1 binds TSC2 and TOR. 2 / 2
| 2
sparser
"We show that Tsc1 and Tsc2 can physically associate with TOR and function upstream of TOR genetically."
sparser
"One possibility is that TOR and TSC1-TSC2 complexes associate with detergent-containing micelles."
TSC1 binds TSC2 and toxB. 2 / 2
| 2
sparser
"P. K. xref showed that two linked recessive genes on chromosome arm 3BL conferred resistance to race 3 (produces Ptr ToxC) and race 5 (produces Ptr ToxB) isolates in tetraploid wheat, indicating that the Tsc1 -Ptr ToxC and Tsc2 -Ptr ToxB interactions were not involved."
sparser
"The Tsn1 -Ptr ToxA, Tsc2 -Ptr ToxB, and Tsc1 -Ptr ToxC interactions have all been shown to play significant roles in the development of tan spot in common (hexaploid) wheat ( T. aestivum L. ssp. aestivum , 2 n = 6 x = 42, AABBDD genomes) ( xref ; xref )."
GAP binds TSC1 and TSC2. 2 / 2
| 2
sparser
"This is accomplished by AKT-1 phosphorylation and inactivation of TSC2 [ xref - xref ], which forms a TSC1TSC2 protein complex that is a GAP for the RHEB G-protein."
sparser
"The C-terminal domain of TSC2 contains a small region of homology with GTPase-activating proteins (GAPs), and TSC1 and TSC2 interact to form a complex that acts as a GAP for the small G-protein RHEB, accelerating the conversion of RHEB from its active GTP-bound state to its inactive GDP-bound form xref ."
TSC1 binds TSC2 and SESN2. 2 / 2
| 2
sparser
"None of these proteins was precipitated by the Flag antibody if they were coexpressed with GFP instead of Sesn2F. Reciprocal immunoprecipitation experiments confirmed the interaction of Sesn2 with TSC[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"None of these proteins was precipitated by the Flag antibody if they were co-expressed with GFP instead of Sesn2F. Reciprocal immunoprecipitation experiments confirmed the interaction of Sesn2 with TSC1, TSC2 and AMPKα2 ( xref )."
sparser
"To determine whether the Sestrins can interact with TSC1, TSC2 or AMPK, we expressed TSC1-Myc, TSC2-HA and AMPKα2-Myc together with Sesn2F in HEK293 cells."
sparser
"Sestrins interact with TSC1, TSC2 and AMPK."
GAP binds RHEB, TSC1, and TSC2. 2 / 2
| 2
sparser
"TBC1D7 knockdown decreases the association of TSC1 and TSC2 leading to decreased Rheb-GAP activity, without effects on the localization of TSC2 to the lysosome."
sparser
"TBC1D7 knockdown using siRNA decreased the association of TSC1 and TSC2 resulting in the decrease of Rheb-GAP activity."
AMPK binds TSC1, TSC2, and MTOR. 2 / 2
| 2
sparser
"The complex of hamartin (TSC1) and tuberin (TSC2) interact with AMPK and mTOR, and mutations in TSC1 or TSC2 lead to uncontrolled cell growth. xref TSC is associated with characteristic neoplasms such as neurofibromas in the skin, angiomyolipoma in the kidney and LAM in the lung."
sparser
"Sestrins inhibit mTORC1 activity by interacting with mTOR pathway suppressors AMPK, TSC1, and TSC2 [ xref ]."
GAP binds mTORC1, RHEB, TSC1, and TSC2. 2 / 2
| 2
sparser
"Most of these signals exert their effect on mTORC1 by modulating the activity of the tuberous sclerosis complex proteins, TSC1 and TSC2, which form a heterodimer that functions as a GTPase activating [MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"Most of these signals exert their effect on mTORC1 by modulating the activity of the tuberous sclerosis complex proteins, TSC1 and TSC2, which form a heterodimer that functions as a GTPase activating protein (GAP) to inhibit the activity of the small GTPase Rheb ( xref )."
Phosphorylated TSC1 binds TSC2. 1 / 1
| 1
reach
"The phosphorylated TSC1 and TSC2 complex inactivates the Rheb GTP component needed for mTOR signaling."
TSC1 binds mutated TSC2. 1 / 1
| 1
reach
"Loss-of-function mutations of the tuberin and hamartin complex impair GTPase activity, leading to constitutive activation of these proteins."
TSC1 bound to TSC2 binds TSC2. 1 / 1
1 |
signor
"TSC1 and TSC2 proteins form a physical and functional complex in vivo. Here, we show that TSC1-TSC2 inhibits the p70 ribosomal protein S6 kinase 1 (an activator of translation) and activates the eukaryotic initiation factor 4E binding protein 1 (4E-BP1, an inhibitor of translational initiation). These functions of TSC1-TSC2 are mediated by inhibition of the mammalian target of rapamycin (mTOR)."
Mutated TSC1 binds TSC2. 1 / 1
| 1
reach
"Inactivating mutations of the TSC1 and TSC2 complex (TSC1/2) cause tuberous sclerosis (TSC), a hereditary syndrome with neurological symptoms and benign hamartoma tumours in the brain."
TSC1 binds TSC2 and PAM. 1 / 1
| 1
sparser
"Our studies show that Pam interacts with the TSC1-TSC2 complex, and regulates mTORC1 signaling [ xref , xref , xref ]."
VEGF binds TSC1 and TSC2. 1 / 1
| 1
sparser
"Loss of the TSC1 or TSC2 gene has been associated with increased production of vascular endothelial growth factor (VEGF), and inhibitors of mTOR have been shown to have an inhibitory effect on production of VEGF, tumor growth, and angiogenesis, both in vitro and in vivo. xref , xref "
TSC1 binds TSC2 and 293T. 1 / 1
| 1
reach
"Consistent with these transfection studies, we could also detect the interaction of endogenous FIP200 with the endogenous TSC1 and TSC2 complex in 293T cells (XREF_FIG E)."
TSC1 binds TSC2 and SIRT1. 1 / 1
| 1
sparser
"Our results demonstrate that SIRT1 and mTOR signaling pathways are indeed interconnected in a way that promotes stress sensing pro-survival signals, where the regulation of mTOR is mediated potentially through an interaction of SIRT1 with the TSC1-TSC2 complex."
TSC1 binds TSC2 and proline. 1 / 1
| 1
reach
"Perhaps the most dramatic metabolic consequence of PI3K and Akt stimulation however, is downstream activation of the cell growth regulator mechanistic target of rapamycin complex 1 (mTORC1) upon Akt mediated phosphorylation of either of two mTORC1 inhibitors : tuberous sclerosis 2 (TSC2; part of the TSC1 and TSC2 complex) or proline rich Akt substrate 40 kDa (PRAS40)."
TSC1 binds TSC2 and casE. 1 / 1
| 1
sparser
"Results showed that TSC1 mutations in the tuberin interaction domain were significantly associated with lower intellectual outcomes (P<0.03), which was also the case for TSC2 protein-truncating and hamartin interaction domain mutations (both P<0.05)."
TSC1 binds TSC2 and YWHAQ. 1 / 1
1 |
hprd
No evidence text available
TGFB1 binds TSC1 and TSC2. 1 / 1
| 1
sparser
"Furthermore, we found that reduced expression of TSC1 and TSC2 caused by TGF-β1 is associated with the promoter methylation status of TSC1 and TSC2."
TSC1 binds TSC2 and TBC1 domain. 1 / 1
| 1
reach
"TSC2 forms a complex with TSC1 and TBC1 domain family member 7 (TSC complex) and acts as a negative regulator of mTORC1 signaling XREF_BIBR, XREF_BIBR, XREF_BIBR."
| 1
sparser
"Also it is suggested that TSC1 interacts with TSC2 to stabilize TSC2 by excluding HERC1 ubiquitin ligase from the TSC2 complex xref ."
TSC1 binds TSC2 and PTK2. 1 / 1
1 |
hprd
No evidence text available
TSC1 binds TSC2 and TRX1. 1 / 1
| 1
sparser
"We showed that pUL38 interacts with TSC1 and TSC2 in cells infected with wild-type cytomegalovirus."
TSC1 binds TSC2 and PAM. 1 / 1
1 |
hprd
No evidence text available
TSC1 binds TSC2 and CDKN1B. 1 / 1
| 1
sparser
"Whereas tuberin also binds p27 in TSC1-negative cells, hamartin does not bind p27 without tuberin."
TSC1 binds TSC2 and RHOA. 1 / 1
| 1
sparser
"Because TSC2 binds TSC1 ( xref , xref ; xref ) by the domain that overlaps the Rho-activating domain of TSC1 and potentially inhibits TSC1-dependent Rho activation, we investigated whether or not stress fiber disassembly involves TSC1."
TSC1 binds TSC2 and PKD1. 1 / 1
| 1
sparser
"Using mouse models, we showed a genetic interaction between Tsc1 and Tsc2 with Pkd1 and confirmed an mTOR-independent pathway of renal cystogenesis."
TSC1 binds TSC2 and FBXW5. 1 / 1
1 |
hprd
No evidence text available
TSC1 binds TSC2 and CTNNB1. 1 / 1
| 1
sparser
"Second, hamartin and tuberin interacts with components of the β-catenin destruction complex, thus regulate Wnt/β-catenin signaling xref ."
TSC1 binds TSC2 and PLK1. 1 / 1
1 |
hprd
No evidence text available
TSC1 binds TSC2 and YWHAZ. 1 / 1
| 1
sparser
"The interaction between tuberin and 14-3-3zeta was confirmed in vitro and by co-immunoprecipitation; multiple sites within tuberin for 14-3-3zeta binding were identified; and it was determined that 14-3-3zeta associated with the tuberin-hamartin complex."
TSC1 binds TSC2 and EGFR. 1 / 1
| 1
sparser
"We then wondered whether expression of hamartin, p-mTOR or p-TSC2 was associated with EGFR-mutations since approximately 20% of adenocarcinoma of the lung patients’ specimens reveal EGFR-mutations [ xref ]."
TP53 binds TSC1 and TSC2. 1 / 1
| 1
sparser
"Further application of full exome and genome sequencing will likely uncover additional evidence of genetic interactions between TP53 and both TSC1 and TSC2 in a variety of human cancers."
TSC1 binds TSC2 and PTEN. 1 / 1
| 1
sparser
"We further demonstrate that Akt/PKB associates with hamartin-tuberin complexes, promoting phosphorylation of tuberin and increased degradation of hamartin-tuberin complexes."
TSC1 binds TSC2 and DOCK7. 1 / 1
1 |
hprd
No evidence text available
TSC1 binds TSC2 and ARSD. 1 / 1
| 1
sparser
"ASD was not associated with TSC1 or TSC2 mutations ( P = 1.0)."
TSC1 binds TSC2 and catenin. 1 / 1
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sparser
"It is interesting to note that the tumor suppressor complex formed by TSC1 and TSC2 interacts with the β -catenin degradation complex and thus modulates the action of Wnt signaling [ xref , xref ]."
TSC1 binds TSC2 and PIK3C3. 1 / 1
| 1
sparser
"Given that TSC1 is required for the stability of TSC2 [ xref ], we hypothesized that binding of VPS34 to TSC1 disengaged TSC1/TSC2 heterodimer, which may lead to degradation of TSC2."
TSC1 binds TSC2 and ATXN3. 1 / 1
| 1
sparser
"PEComas are related to the genetic alterations of tuberous sclerosis complex (TSC), an autosomal dominant genetic disease associated with losses of TSC1 (9q34) or TSC2 (16p13.3) genes, which seem to have a role in the regulation of the Rheb/mTOR/p70S6K pathway."
TSC1 binds TSC2 and Hsp90α. 1 / 1
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sparser
"Surprisingly, direct interaction of Tsc2 and Hsp90α‐His 6 did not occur in vitro ; however, pre‐incubation of Hsp90α‐His 6 with Tsc1 facilitated the formation of Hsp90α:Tsc1:Tsc2 complex (Fig  xref F)."
HSP90 binds TSC1 and TSC2. 1 / 1
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sparser
"To determine Tsc1 and Tsc2 interaction with these Hsp90 domains, we transiently transfected and expressed each domain with FLAG‐tag in HEK293 cells."
ERK binds TSC1 and TSC2. 1 / 1
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sparser
"As a result, upon abrogation of basal levels of Erk activity, wild-type TSC2 binds TSC1 as strongly as TSC2 S664A/S540A , suggesting that the observed stronger interaction between TSC1 and the TSC2 S6[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
TSC1 binds TSC2 and RICTOR. 1 / 1
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sparser
"However, when either mTOR or mSin1 were omitted, only Rictor bound to the TSC1-TSC2 complex, demonstrating that Rictor is sufficient for the association."
TSC1 binds TSC2 and D1. 1 / 1
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reach
"It was suggested that TSC1 and TSC2 complex may regulate Cyclin D1 expression through canonical Wnt and beta-catenin signaling."
TSC1 binds TSC2 and CCND1. 1 / 1
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hprd
No evidence text available
TSC1 binds TSC2 and PLK2. 1 / 1
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"We have demonstrated that Plk2 interacts with both TSC1 (endogenous, CT-Plk2) and TSC2 (CT-Plk2) in various cell types."
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"Previous work has also shown that Tsc1 and Tsc2 both interact with the co‐chaperone complex R2TP/Prefoldin‐like (R2TP/PFDL) complex (Cloutier et al , xref )."
RHEB binds TSC1, TSC2, and MTOR. 1 / 1
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"Full-length TSC2 protein interacts with TSC1 to inhibit the activation of mTOR by Rheb."
TSC1 binds TSC2, MTOR, and cKO. 1 / 1
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"The global follicle activation phenotype previously documented in Tsc1 or Tsc2 cKO females was associated with dramatic upregulation of the mTOR signaling pathway (demonstrable with the same immunohistochemical assays performed in our study) ( xref , xref ), yet Rheb conditional inactivation in oocytes did not have any observable effect on follicle maturation."
GST binds TSC1, TSC2, and TBC1D7. 1 / 1
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sparser
"Furthermore, the pull-down analysis showed that both of TSC1 and TSC2 obtained from HEK293 cells bound to the bacterial GST-TBC7 in a dose-dependent manner, but not to the control protein (D)."
sparser
"Next, we co-transfected HeLa cells with different forms of myc-TSC1 with HA-TSC2 and treated with nocodazole."
GST binds TSC1, TSC2, and PLK2. 1 / 1
| 1
sparser
"Additionally, C-terminal Plk2-GST fusion protein bound both TSC1 and TSC2 proteins."
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"Since in control experiments, Tsc1 and Tsc2 do not bind to Luciferase or GST, respectively (Figure 4) , the binding between Tsc1 and Tsc2 was unlikely due to nonspecific sticking."
TSC1 binds TSC2, PEX19, and Flag. 1 / 1
| 1
sparser
"While a very small amount of Flag-TSC2 was associated with the PEX19-TSC1 complex ( xref ), this association was abrogated with the TSC2-G294E mutant (a TSC1 binding-deficient mutant xref ), indicating the little TSC2 detected in this complex was likely associated with TSC1, rather than directly bound to PEX19 ( xref )."
TSC1 binds TSC2, MMP2, and PHEX. 1 / 1
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sparser
"Here we show that TSC1 and TSC2 associate with PEX proteins and are localized to peroxisomal membranes, where they regulate mTORC1 signaling in response to ROS."
MTORC1 binds RHEB, TSC1, and TSC2. 1 / 1
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sparser
"Loss-of-function TSC1 or TSC2 mutations are associated with increased Rheb-GTP levels and aberrant activation of mTORC1 in various TSC-associated hamartomas ( xref , xref )."
MTORC1 binds TSC1, TSC2, and NCAPD2. 1 / 1
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sparser
"The finding of the association of mTORC1 with the bipartite complex TSC1 and TSC2 of tumor suppressor proteins provided a molecular link between mTOR and cancer (reviewed in REF xref )."
TSC1 binds TSC2, RB1CC1, and MEF. 1 / 1
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sparser
"Together, these results demonstrate that FIP200 could associate with the TSC1TSC2 complex in mammalian cells such as 293T cells and MEFs."
TSC binds TSC1, TSC2, and MTOR. 1 / 1
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sparser
"TSC is associated with mutations in TSC1 or TSC2, resulting in hyperactivation of mTOR complex 1 (mTORC1)."
TSC1 binds TSC2, GSK3B, and AXIN1. 1 / 1
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hprd
No evidence text available
TSC binds TSC1, TSC2, and TBC1D7. 1 / 1
| 1
sparser
"This interaction is inhibited by the Rheb-GTPase activating protein (GAP) activity of the tuberous sclerosis protein complex (TSC) that is formed by the TSC1, TSC2 and TBC1D7 proteins [ xref ]."
AMPK binds TSC1, TSC2, and SESN2. 1 / 1
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"To study whether a complex containing Sesn2, TSC1, TSC2 and AMPK can form under more physiological conditions, we immunoprecipitated lysates of MCF7-tet OFF Sesn2F or MCF7-tet OFF GFP cells with the Flag antibody."
TSC1 binds TSC2, STRADA, and PTEN. 1 / 1
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sparser
"Among these, TSC1, TSC2, STRADα and PTEN are associated with epilepsy and autism in humans and animal models."
sparser
"The TSC1 and TSC2 proteins assemble into a complex that is stabilized by TBC1D7 through its direct interaction with the TSC1 coiled coil (CC) region."
AXIN binds Wnt, TSC1, TSC2, and CTNNB1. 1 / 1
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sparser
"Both TSC1 and TSC2 are able to associate with Axin and β-catenin in the canonical Wnt pathway, and an absence of either TSC1 or TSC2 has shown to increase Wnt signaling ( Mak, Takemaru, Kenerson, Moon[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
| 1
sparser
"Likewise, we find increased binding of TSC2, TSC1 and TBC1D7 to the Rag GTPases in response to various stresses ( xref ), in agreement with relocalization of the entire TSC complex to lysosomes."
TSC1 binds TSC1, TSC2, TSC2, and ATXN3. 1 / 1
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"TSC is an autosomal dominant disease that is associated with gene mutations of TSC1 or TSC2 , encoding hamartin and tuberin, respectively [ xref ]."
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hprd
No evidence text available
TSC binds TSC1, TSC1, TSC2, and TSC2. 1 / 1
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sparser
"Genetically, TSC is associated with mutations in TSC1 or TSC2 (located on 9q 34 and 16q13 respectively), leading to impaired production of the proteins hamartin and tuberin respectively."
AMPK binds TP53, TSC1, TSC2, and MTOR. 1 / 1
| 1
sparser
"The antioxidant response of p53 also inhibits the mTOR pathway via the Sestrins, which are induced by p53 and can interact with mTOR pathway suppressors AMPK, TSC1 and TSC2 [ xref ]."
sparser
"Tuberous sclerosis complex is exclusively associated with mutations in either the TSC1 or TSC2 tumour suppressor gene, which encodes the proteins hamartin and tuberin, respectively."
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hprd
No evidence text available
RB1CC1 affects TSC1, and TSC2
1 | 21
1 | 21
sparser
"Indeed, the FIP200 N1-859 fragment, which can interact with the TSC1TSC2 complex ( xref A), showed similar activity as the full-length FIP200 in the inhibition of cell cycle progression as measured by BrdU incorporation (not depicted)."
sparser
"Similar studies indicated that the N1-859 segment of FIP200, but not the N1-638 segment, which does not bind to TSC1TSC2, also increased the average cell size of the transfected 293T cells ( xref )."
sparser
"FIP200 interaction with the TSC1TSC2 complex is not involved in FIP200 regulation of cell cycle progression."
sparser
"Together, these data suggest that interaction between FIP200 and the TSC1TSC2 complex is not involved in FIP200-mediated cell cycle progression."
sparser
"We found that association of FIP200 or its segments N1-859 and N1-638 with the TSC1TSC2 complex correlated with their ability to increase cell size, up-regulate S6K phosphorylation, and decrease TSC1–TSC complex formation."
sparser
"Association of FIP200 with the TSC1TSC2 complex."
sparser
"Together, these data suggest that FIP200 interaction with the TSC1TSC2 complex is not required for FIP200 regulation of cell cycle progression."
sparser
"Consistent with these transfection studies, we could also detect the interaction of endogenous FIP200 with the endogenous TSC1TSC2 complex in 293T cells ( xref E)."
sparser
"These results suggest that FIP200 interaction with the TSC1TSC2 complex might not be required for FIP200 regulation of cell cycle progression."
sparser
"Therefore our identification of the interaction between FIP200 and the TSC1TSC2 complex raises the interesting possibility that FIP200 may regulate cell size through interaction with the TSC1TSC2 complex."
TBC1D7 affects TSC1, and TSC2
1 | 12 8
1 | 12 8
reach
"The TSC1, TSC2, and TBC1D7 complex is the critical negative regulator of mTORC1 signalling with respect to most of its upstream regulators, such as growth factors, insulin and energy levels [XREF_BIBR]."
reach
"Complete loss of either TSC1 or TSC2 inactivates the TSC1, TSC2, and TBC1D7 complex leading to constitutive high-level activation of mTORC1 in TSC tumors."
reach
"Hence, exogenous expression of TSC1, as effected here by infection with a gene therapy vector can serve to rescue normal levels of the TSC1, TSC2, and TBC1D7 complex."
sparser
"The TSC complex, formed by the subunits TSC1, TSC2, and TBC1D7, is responsible for relaying most growth factor signaling pathways to mTORC1 (Ben‐Sahra & Manning, xref )."
sparser
"TSC1, TSC2, and TBC1D7 form a heteromeric complex that can bind to and stimulate the GTPase Ras homolog enriched in brain Rheb ( xref ; xref ; xref ; xref ) (for reviews see ( xref ; xref ) ( xref )."