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TSC1 inhibits MTOR. 166 / 174
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"In this regard, S6K is regulated by mTor, which is inactivated by the TSC1 and TSC2 tumor suppressors (Inoki et al., 2005; Manning and Cantley, 2003; Nobukini and Thomas, 2004)."
16517408
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"Nevertheless, the ability of the Rheb-GAP, TSC1 and TSC2, to inhibit mTOR signaling in vivo is consistent with the inference that Rheb-GDP provides a less effective stimulus than Rheb-GTP."
15854902
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"Loss of TSC1 leads to mTOR mediated inhibition of PI3K-AKT in naive CD8 + T cells."
22363451
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"XREF_BIBR Both sestrins can trigger the AMPK and target it to phosphorylate and activate TSC1 and TSC2 complex, thereby inhibiting the signaling of mTOR, a critical autophagy inhibitor of cells, XREF_BIBR, XREF_BIBR and so CX-5461-induced autophagy through AMPK and mTOR signaling pathway in U2-OS cells might arise from the upregulation of Sesn1/2 by p53."
27729807
sparser
"This mechanism of p53-induced autophagy involves activation of 5′ AMP-activated protein kinase (AMPK) as well as the tuberus sclerosis complex kinases, TSC1 and TSC2, which finally inhibit mTOR kinase."
27601937
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"In the majority of cells under stress conditions, activation of AMPK phosphorylates TSC2 leading to TSC1 and TSC2 dependent suppression of mTOR to inhibit cell proliferation [XREF_BIBR, XREF_BIBR]."
27258250
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"Interestingly, in 2001 and 2002, TSC1 and TSC2 were shown to canonically modulate the serine threonine kinase mechanistic target of rapamycin (mTOR), within the insulin growth factor (IGF) signaling pathway."
33052752
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"Constitutive mTOR activation by loss of TSC1 and TSC2 rapidly stimulates the targets of both PERK and IRE1, which UPR activation could not be observed in combined treatment of TSC1 and TSC2 depletion and rapamycin addition."
27992581
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"Two of these genes, TSC1 and TSC2, are downstream of AMPK and negatively regulate mTOR in response to cellular energy deficits."
24612911
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"AKT activation leads to cell growth by activating mTOR through TSC1/2 phosphorylation, while increased levels of TSC1 and TSC2 inhibit the mTOR pathway; mTOR positively regulates 4E-BP1 and p70S6k, which are activated in a variety of cancers."
33805447
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"TSC1 and TSC2 are downstream of AMPK and negatively regulate mTOR in response to cellular energy deficit."
20448661
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"MTOR is inhibited upon withdrawal of growth factors, such as insulin or insulin like growth factors, by a cascade of phosphorylation reactions involving Class I PI3K, Akt, TSC1 and TSC2, and Rheb."
22661635
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"In evaluating the mechanism of increased mTOR activity documented in gliomas, we asked whether decreased expression levels of hamartin and tuberin may relieve the inhibitory control of mTOR and lead to elevated mTOR activity."
18759130
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"Cell growth is positively regulated by mTOR, whose activity is inhibited by the TSC1 : TSC2 complex."
18692468
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"AMPK promotes autophagy by at least the following ways : phosphorylating the tuberous sclerosis (TSC) complex proteins TSC1 and TSC2, which in turn downregulate mTOR activity and induce autophagy 59, phosphorylating FOXO3, phosphorylating ULK1, and dissociating Beclin1 and Bcl-2 by stimulating JNK1-Bcl-2 signaling XREF_BIBR - XREF_BIBR."
29396411
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"These results suggest that the selective deletion of Tsc1 in OLs resulted in activation of the mTOR pathway."
27416896
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"Particularly, pathogenic variants in TSC1 that inhibit MTOR activity underlies the Tuberous Sclerosis Complex (TSC)."
33071758
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"Thus, loss of either TSC1 or TSC2 leads to unchecked activation of mTOR."
34259631
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"TSC derives from inactivating mutations of either the TSC1 or TSC2 tumor suppressor gene, and the resulting inactivation of the TSC1 and TSC2 protein complex causes hyperactivation of the mammalian target of rapamycin (mTOR), leading to uncontrolled cell growth and proliferation."
19539245
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"In addition, loss of chromosome 9 is frequent, targeting CDKN2A at 9p21 (encoding the cell cycle regulator p16 INK4A and the activator of p53 p14 ARF) and various genes on 9q, such as TSC1 (an inhibitor of mTOR)."
21457491
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"XREF_BIBR TSC2 : TSC1 inhibits mTOR activity by stimulating the conversion of active Rheb-GTP to the inactive form, Rheb-GDP."
20146692
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"While transcripts for Tsc1 that is an upstream negative regulator of mTOR signaling [XREF_BIBR] were highly reduced in Foxo3 mutant erythroblasts (XREF_FIG), TSC1 protein was not significantly altered (XREF_FIG, quantification in the right panel) suggesting that reduction of TSC1 transcript expression was unlikely to mediate activation of mTOR in Foxo3 mutant erythroblasts."
24966026
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"At the molecular level, TSC is caused by either the loss or malfunction of either hamartin (TSC1) or tuberin (TSC2), which interact in a heterodimer known as the TSC1 and TSC2 complex, to negatively regulate mammalian target of rapamycin complex 1 (mTORC1)."
22198573
sparser
"This can stimulate autophagy by activating AMPK or by upregulating phosphatase and tensin homologue (PTEN, a PIP 3 3′ phosphatase) and TSC1 which inhibits mTOR."
20188203
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"Tuberous Sclerosis Complex (TSC) is caused by TSC1 or TSC2 mutations, resulting in hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1)."
34253722
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"Since hamartin and tuberin negatively regulate mTOR activity, which in turn phosphorylates and thereby activates important translation factors such as p70 S6 kinase 1 (S6K1) and eukaryote initiation factor 4E binding protein (eIF4E-BP), a major role of the TSC-mTOR signaling pathway has been suggested for tumorigenesis, and both genes were initially recognized as tumor suppressors [XREF_BIBR]."
22848848
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"Thus, release of TSC1-dependent mTOR inhibition is sufficient to initiate prostate tumor progression."
30733194
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"The mutations of either TSC1 or TSC2 gene activate the mammalian target of rapamycin (mTOR) signaling pathway, resulting in cellular aberrant function and tumor growth [XREF_BIBR, XREF_BIBR]."
30107845
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"Here we report that, unexpectedly, constitutive activation of mTOR signalling by Tsc1 deletion in the oligodendrocyte lineage results in severe myelination defects and oligodendrocyte cell death in mice, despite an initial increase of oligodendrocyte precursors during early development."
27416896
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"The TSC1/TSC2 complex is the main upstream regulator of mTOR, and hyperactivated mTOR, caused by the loss of TSC1 or TSC2, leads to uncontrolled cell proliferation and tumor growth [31]."
34341336
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"According to a model based on these data, in the absence of growth factors the TSC1 and TSC2 complex is hypophosphorylated and inhibits mTOR."
12935885
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"Tuberous sclerosis is a genetic condition resulting from mutations in the TSC1 or TSC2 gene, which negatively regulate mTOR activity."
26403076
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"Our finding that TNFalpha mediates tumor angiogenesis through dysregulated mTOR signaling caused by suppression of TSC1 by IKKbeta reveals a novel mechanism of inflammation mediated tumor angiogenesis[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
17693255
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"ERK-dependent phosphorylation of tuberin prevents its association with hamartin and the inhibition of Rheb and mTOR by the tuberin-hamartin complex."
20219622
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"The heterodimer of TSC2 (tuberin) and TSC1 (hamartin) represses mTOR activity by acting as the GTPase-activator protein for the small G protein Rheb (Ras homolog enriched in brain), a potent activator of mTORC1 when present in a GTP bound state."
20388847
eidos
"AKT activates mTOR by inhibiting the formation of TSC1 / TSC2 composite and PRAS40 , an important negative regulatory factor in this pathway 78 ."
32047547
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"MTOR activity is negatively regulated by the heterodimer TSC1 (hamartin) and TSC2 (tuberin)."
21765994
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"Because TSC1 functions as a complex with TSC2 to inhibit mTOR signaling by preventing the degradation of TSC2 28, we first investigated whether overexpression of TSC1 leads to stabilization of TSC2 in Tsc1 tg mice."
28400571
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"One possibility was that forebrain Tsc1 deletion was driving an increase in mTOR activity."
25315683
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"Mutations in either TSC1 or TSC2, which encode hamartin and tuberin, respectively, cause the abnormal activation of mammalian target of rapamycin (mTOR)."
25574245
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"Recently, the TSC1 and TSC2 protein complex was shown to inhibit the kinase mTOR (mammalian target of rapamycin)."
15856327
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"Therefore, loss-of-function mutations or removal of PTEN, which leads to hyperactivation of Akt, or loss of TSC1 and TSC2, which leads to increased unbound RHEB, can cause an upregulation of mTOR signaling."
24672426
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"Tsc1 deletion should be sufficient to activate the mTOR pathway."
29483507
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"Recently, mTOR activation by Pten or Tsc1 knockout was shown to promote the regenerative capacity of injured axons XREF_BIBR."
20062052
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"TSC1 and TSC2 inhibit mTOR signaling via direct inhibition of the Ras homolog enriched in brain, Rheb."
29709573
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"These tumors are characteristically driven by deleterious mutations in the tumor suppressors TSC1 and TSC2, whose gene products typically act to inhibit mTOR."
30285856
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"In the presence of growth factors such as insulin or insulin like growth factors, stimulated Akt and extracellular signal regulated protein kinases 1 and 2 (ERK1/2) can phosphorylate and disrupt the tuberous sclerosis complex 1/2 (TSC1 and TSC2), which activates mTOR inhibition and thus inhibiting autophagy [XREF_BIBR]."
28534010
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"Cardiac Tsc1 deletion (T1-hKO) caused mouse mTOR activation and cardiomyopathy."
34101831
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"The pathophysiology of TSC mainly involves the hyperactivation of mammalian target of rapamycin (mTOR) induced by TSC1 (hamartin) and TSC2 (tuberin) heterozygosity."
32071825
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"In wild-type adult mice, the regeneration failure may be contributable to the suppression of mTOR activity and new protein synthesis in axotomized RGCs, since reactivating this pathway by conditional knockout of TSC1, which negatively regulate the mTOR pathway, leads to axon regeneration [XREF_BIBR]."
21307646
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"TSC1 is an inhibitor of mTOR an important signaling mediator downstream of PI3K and AKT a major growth and survival pathway in angiogenesis."
31045327
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"Two tumor suppressors in the PI3K-mTOR pathway altered in the majority of human gliomas XREF_BIBR - XREF_BIBR, PI3K regulatory subunit pi3kr1 and the tsc1 repressor of mTOR, were decreased in expression level in the Tg (flk1 : RFP) is18 tumors (XREF_FIG and XREF_SUPPLEMENTARY)."
25485542
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"TSC1/2 form a protein complex that negatively regulates mTOR signaling, and loss of either TSC1 or TSC2 leads to constitutive activation of the mTOR pathway."
18988856
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"Loss of a functional hamartin and tuberin complex leads to increased activation of mTOR signaling and subsequent unregulated cell growth and proliferation."
27898583
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"Therefore, homozygous loss of TSC1 or TSC2 leads to high constitutive activation of mTOR signaling, as detected in mouse embryonic fibroblasts, in the tumors of rodent models of TSC, and in human TSC cells and tumors."
15533996
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"These data indicate that deletion of TSC1 results in activation of mTOR signaling in the pancreas of Neurog3-Tsc1-/-(TN) mice."
25425965
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"Mutations in the TSC1 or TSC2 genes lead to disruption of the TSC1-TSC2 intracellular protein complex, causing overactivation of the mammalian target of rapamycin (mTOR) protein complex."
26067126
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"Deletion of tuberous sclerosis complex 1 (TSC1), a negative regulator of mTOR, also activated mTOR and enhanced axon regeneration principally by mimicking the effect of PTEN deficiency [XREF_BIBR]."
24630093
eidos
"Their products , hamartin and tuberin , act as a complex to inhibit mTOR signaling ."
30657883
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"TSC1 and TSC2, which inhibit mTOR signaling, are known as important regulators of cell size and growth [XREF_BIBR, XREF_BIBR]."
24167408
sparser
"Rapid advances in our knowledge of TSC were catalyzed by the discovery that hamartin-tuberin normally inhibits the mechanistic target of rapamycin (mTOR; previously known as mammalian target of rapamycin) serine/threonine kinase ( xref )."
23580196
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"Also, TSC1, in coordination with TSC2, inhibits MTOR, which promotes cell growth and cell cycle progression [XREF_BIBR]."
28122328
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"We found that TSC2, but not TSC1, Rheb, or mTOR itself, associated with GST-ARD1 (XREF_FIG), suggesting that TSC2 may be involved in ARD1 mediated mTOR inhibition."
20145209
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"Conversely, mTOR hyper activation by Tsc1 deletion results in a rapid exit from quiescence and cell cycle entry, which is accompanied by an increase in mitochondrial biogenesis and ROS levels."
24768033
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"To ensure that lack of competitiveness was not a result of the supra-physiological activation of mTOR driven by deletion of Tsc1, we performed a similar set of experiments using mice engineered to express a constitutively active allele of the RagA (Rraga) GTPase, Rraga Q66L (referred to hereafter as Rraga GTP)."
28636954
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"Based on our findings, it is likely that TSC1, which negatively regulates mTOR in complex with TSC2, also regulates HIF, but this remains to be proven.The induction of Hif-1alpha protein and Hif respo[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
12957289
sparser
"The tuberin-hamartin protein complex inhibits mTOR (a key protein in the regulation of cell cycle) through the so-called S6 ribosomal kinase plus eIf4EEI- and 4E-binding protein [ xref ] (suppressors of the initiation factor for protein synthesis)."
23401839
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"Local cap dependent mRNA translation is also controlled by mammalian target of rapamycin (mTOR), which in turn is negatively regulated by the tuberous sclerosis complex proteins TSC1 and TSC2."
27669991
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"Activation of mTOR by loss of the inhibitory TSC1 and TSC2 function resulted in decreased NF-kappaB activity in mouse embryonic fibroblasts."
29768212
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"TSC2 is a tumor suppressor that has been linked to AMPK and it forms an inhibitory complex with TSC1 that binds to and inhibits mTOR, leading to negative regulation of cell size and growth."
21618507
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"TSC2 : TSC1 is also inhibited by the binding of forkhead transcription factor (FoxO1) to TSC2, ultimately activating the mTOR signaling cascade."
28053551
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"We confirmed that conditional loss of Tsc1 resulted in upregulation of the mTOR pathway in hippocampal neurons."
21677170
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"Hamartin and tuberin act as a complex upstream of mTOR and inhibit the mTOR pathway via inhibition of Rheb (Ras homolog enriched in brain) (XREF_FIG)."
22544534
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"Activation of AMPK modulates insulin signalling downstream of the insulin receptor [XREF_BIBR], most notably via differentially phosphorylating the tuberous sclerosis complex TSC1 and TSC2 to inactivate mTOR [XREF_BIBR, XREF_BIBR]."
22548055
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"Using this approach, we propose a network model illustrating the linkage between hyperactivated mTOR signaling caused by TSC1 deletion and morphological and developmental defects in the telencephalon."
28588230
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"Surprisingly, however, deletion of TSC1, also expected to enhance mTOR signaling in the same neuronal population, led to hyperphagia and obesity, suggesting that LKB1 may engage other signaling pathways to influence the activity of these and associated neurons in the melanocortin network."
20354156
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"As such, loss of either TSC1 or TSC2 leads to mTOR activation."
23063455
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"The mTOR pathway is negatively regulated by tumor suppressor genes TSC1 and TSC2, as well as by their upstream regulators including phosphatase and tensin homolog (PTEN), the STE20 related kinase adaptor alpha (STRADalpha and neurofibromin 1 (NF1) (XREF_FIG)."
22578218
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"XREF_BIBR TSC1 or TSC2 depleted cells fail to attenuate downstream mTOR signaling in response to amino acid depletion, serum starvation or growth factor withdrawal."
20146692
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"Both proteins TSC1 and TSC2 downregulate mTOR, which eventually lead to the promotion of autophagy [XREF_BIBR - XREF_BIBR]."
26934368
sparser
"The TSC1-TSC2 complex inhibits mTOR complex 1 (mTORC1), which functions to promote protein synthesis and cell growth."
24448243
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"It is caused by mutations in the TSC1 or TSC2 tumor suppressor genes, resulting in hyperactivation of the mechanistic target of rapamycin (mTOR) signaling pathway and subsequent cell cycle dysregulation."
26365597
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"Loss of Tsc1 and Tsc2 activates mTOR and disrupts PI3K-Akt signaling through downregulation of PDGFR."
14561707
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"Unexpectedly, however, the LeBrun-Julien et al., (2014) study and other studies on Tsc1 loss in oligodendrocytes demonstrate that hyperactive mTOR signaling driven by loss of Tsc1 results in hypomyelination, with reduced myelin protein and RNA expression, and eventual oligodendrocyte apoptosis."
34110985
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"When either PTEN or TSC1 were silenced in order to reactivate the mTOR pathway, it led to induction of extensive axon regeneration in adult neurons."
22449213
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"Previous study suggested that IKKβ promotes mTOR pathway by deactivating TSC1, which suppresses Rheb and subsequently deactivates mTORC1 [16]."
33469229
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"Our results show that loss of Tsc1 function, through targeted genetic deletion or RNA interference induces an mTOR-dependent hyperproliferative phenotype in post-natal BM-MSCs."
32927859
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"Loss of TSC1 or TSC2 leads to hyperactive mTOR signaling, which is the main cause of tumor growth in TSC patients, and the decreased AKT1 activity due to the negative feedback regulation of mTOR may account for the benign nature of TSC tumors."
23108404
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"TSC1 or TSC2 mutations cause Tuberous Sclerosis Complex (TSC), and lead to mechanistic target of rapamycin (mTOR) hyperactivation evidenced by hyperphosphorylation of ribosomal S6 protein and 4 elongation factor binding protein (4E-BP1)."
32781001
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"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."
19725049
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"Taken together, we showed both spontaneous activation and loss of cellularity of naive T cells after activation of mTOR by Tsc1 deletion."
21709159
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"Tuberous sclerosis complex (TSC) is a genetic disorder caused by mutations in TSC1 or TSC2 resulting in hyperactivity of the mammalian target of rapamycin and disabling brain lesions."
23349360
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"Indeed, DC loss upon TSC1 deficiency is accompanied by increased DC apoptosis and enhanced metabolic activity due to TSC1-dependent inhibition of Myc, an effector downstream of mTOR (Figure 1), and reversed upon Myc loss (35)."
31073300
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"Tuberous sclerosis complex (TSC) is a congenital disorder characterized by cortical malformations and concomitant epilepsy caused by loss-of-function mutations in the mTOR suppressors TSC1 or TSC2."
33786950
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"Tsc1 deletion can result in activation of the mTOR signaling pathway [XREF_BIBR, XREF_BIBR]."
26382847
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"Loss of TSC1 or TSC2 function therefore causes activation of mTOR Complex 1 (mTORC1)."
26235615
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"TSC is an ASD caused by variants in the genes encoding TSC1 or TSC2, two proteins that normally inhibit the mTOR pathway."
31495451
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"While we observed no change in total tuberin expression, there was increased hamartin expression in both Nf1-/- TVZ NSCs and o-GSCs, and a decrease in phosphorylation mediated tuberin inactivation (Ser 939 and Thr 1462), excluding tuberin and hamartin mediated mTOR activation as the mechanism underlying the increased mTOR activity in o-GSCs (XREF_SUPPLEMENTARY)."
25772366
reach
"SESN2 activates AMPK that promotes phosphorylation of the TSC1 : TSC2 complex and finally inhibits mTOR [16]."
27840318
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"This proliferation of smooth muscle like cells is reported to be due to the activation of mammalian target of rapamycin (mTOR) caused by mutations in the tuberous sclerosis complex 1 (TSC1) or TSC2 genes."
29021448
trips
"Hamartin and tuberin, the products of TSC1 and TSC2, respectively, form heterodimers and inhibit the mammalian target of rapamycin."
16339216
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"Activation of gastric mTOR signaling by TSC1 knockdown decreases ghrelin, food intake, body weight and hepatic lipid content."
30141265
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"In mice with conditional TSC1−/− (an inhibitor of mTOR) deletion, greater cellular senescence along with downregulated autophagy proteins were noted in airway endothelial cells or alveolar epithelial cells [52]."
33387604
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"It is caused by mutations in TSC1 or TSC2 genes causing hyperactivation of the mammalian target of rapamycin (mTOR) pathway."
31335226
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"Knockout of alphaB-crystallin and hspB2 reversed deficient Tsc1 mediated fetal gene expression, mTOR activation, mitochondrial damage, cardiomyocyte vacuolar degeneration, cardiomyocyte size, and fibrosis of T1-hKO mice."
34101831
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"The Tsc1 and Tsc2 complex interacts with PI3K and Akt signaling such that inhibition of TSC1 and TSC2 activates mTOR and disrupts PI3K-Akt signaling."
26010875
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"This network model shows that mTOR complex 1 (mTORC1), unlike the mTORC2, would be activated by TSC1 deletion."
28588230
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"Polycystin-1 and the TSC1 and TSC2 tumor suppressor complex both act to suppress the activity of mTOR."
29479522
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"Incubation of RMCs with 1,25 (OH) 2 D 3 for 48 h increased VDR expression (p < 0.05), restored the expression of TSC1 and TSC2 and 4E-BP1, and blocked the aberrant upregulation of Rheb, mTOR and p70S6K."
29416624
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"XREF_BIBR TSC1 and TSC2 mutations impair regulation of the mTOR pathway and cause tuberous sclerosis."
25003006
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"It is also possible that loss of Tsc1 causes mTOR independent alterations in neurons that could affect the actin cytoskeleton or receptor trafficking resulting in disruption of mGluR-LTD."
21677170
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"In normal conditions, mTOR activity is inhibited by proteins hamartin and tuberin that are encoded by TISC1 and TISC2 genes."
20618393
reach
"We hypothesized that Tsc1 normally represses PV-like/FS properties in SST+ CINs by inhibiting MTOR activity."
31676823
reach
"Moreover, in at least some experimental conditions, TSC1, a component of the TSC1/2 (hamartin and tuberin) complex that negatively regulates mTOR pathway, has been shown to localize to the basal body, and loss of either TSC1 or TSC2 upregulates ciliogenesis XREF_BIBR, XREF_BIBR, XREF_BIBR."
27634431
reach
"They performed whole genome sequencing on the patient 's archival tumor and identified a point mutation in TSC1, a tumor suppressor gene that negatively regulates MTOR signaling."
26528881
reach
"The tuberous sclerosis 1 (TSC1) and TSC2 complex negatively regulates the activity of an mTOR containing multiprotein complex called mTOR complex 1."
24818661
reach
"The inactivation of TSC2 leads to proteasomal degradation of the TSC1 and TSC2 protein complex which in turn activates the mammalian target of rapamycin (mTOR) activation."
27242542
reach
"Tsc2 forms a TSC complex with Tsc1, which inhibits mTOR signaling ."
34497307
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"The distinguished role of PTEN for neuronal cell survival was underlined in studies where a conditional deletion of PTEN or Tsc1 was used to increase mTOR activity in RGC after ON lesion."
22065949
reach
"GTP bound Ras homolog enriched in brain (Rheb) is a necessary mTOR activator that is inhibited by tuberous sclerosis complex 1 (TSC1) and tuberous sclerosis complex 2 (TSC2)."
29515798
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"TSC1 is a suppressor of mTOR."
31552471
reach
"Mutations in either of the two tumor-suppressor genes, TSC1 on chromosome 9q34 and TSC2 on chromosome 16p13.3, which encode proteins hamartin and tuberin respectively, disrupt mTOR regulated cellular [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"
30279084
reach
"This is caused by inactivation of TSC1 and TSC2, thus inhibiting PI3K and mTOR signaling downstream of AKT1."
32537434
reach
"In angiosarcomas, Tsc1 deletion enhances mTOR complex 1 (mTORC1) activation through increased expressions of c-Myc and Hif1alpha."
30733194
reach
"When upstream signals are activated, TSC1 and TSC2 is inhibited by AKT, allowing mTOR activation."
26458815
reach
"In particular, conditional deletion of Tsc1 in interneuron progenitors increased mTOR signaling in GABAergic interneurons, leading to loss of interneuron subtypes, lower convulsant induced seizure threshold, and early mortality [XREF_BIBR]."
26517286
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"These results indicate that the mTOR signaling pathway activated by Tsc1-deficiency in CACL1-111 cells was suppressed by restoration of TSC1 expression XREF_BIBR."
23355874
reach
"As TSC1 inhibits mTOR activity in naive T cells through the tuberous sclerosis complex, AMPK restricts the engagement of metabolic programs associated with clonal expansion."
24133495
sparser
"The fragile X mental retardation protein (FMRP), an RNA binding protein, as well as hamartin (TSC1) and tuberin (TSC2) complex that inhibits the mammalian target of rapamycin (mTOR), regulate local protein synthesis at synapses."
30345165
reach
"In such cases loss of TSC1 and TSC2 would be required to activate mTOR."
18759130
sparser
"When present as a heterodimer the TSC1-TSC2 complex inhibits mTOR indirectly by converting the small GTPase Ras homolog enriched in brain (Rheb) to an inactive GDP bound form."
19795384
reach
"The TSC1 and TSC2 proteins negatively regulate mTOR Complex 1 (mTORC1) by inhibiting Rheb activity [XREF_BIBR]."
22018000
reach
"In conclusion, our study revealed that CXXC5-mediated TSC1 suppression activates the mTOR pathway, reduces autophagic cell death, induces PD-L1-mediated immune suppression, and results in tumor development, shedding light on the mechanism of the pathophysiological function of CXXC5."
36539038
reach
"Moreover, neuronal loss-of-function of Tsc1 led to an mTOR dependent increase in AMPA receptor surface expression, possibly mediated by an mTOR dependent increase in local dendritic synthesis of AMPA receptors."
19694899
sparser
"The hamartin–tuberin complex normally inhibits mammalian target of rapamycin complex 1 (mTORC1) in a cell."
34178582
reach
"Further studies showed that constitutive activation of mammalian target of rapamycin complex 1 (mTORC1) by TSC1 deletion specifically in the myeloid lineage regulated FABP4 expression in macrophages to exacerbate RA progression in mice."
35729106
sparser
"P53 is linked to autophagy via inhibition of mTOR by AMPK, TSC1, and TSC2, and plays a important role in the transcriptional regulation of autophagy-related target genes ( xref )."
29430945
reach
"TSC is caused by mutations in the TSC1 or TSC2 gene resulting in activation of the mechanistic target of rapamycin (mTOR) signaling pathway."
30976976
reach
"Although it is clear that growth factor induced activation of Akt blocks TSC1 and TSC2 inhibition of mTOR signaling [XREF_BIBR - XREF_BIBR], the molecular mechanism by which Akt inhibits the function of TSC1 and TSC2 protein complex as a cell growth suppressor is still undefined."
20412061
reach
"The relevance of the mTOR pathway in the pathophysiology of TSC was first suggested in simplified biological systems, such as drosophila and yeast, in which hamartin and tuberin were shown to inhibit mTOR signaling."
23644232
reach
"TSC1 conditional knockout (DMP1-Cre+; TSC1 f/f , hereafter CKO) mice were generated to increase the activity of mechanistic target of rapamycin complex 1 (mTORC1)."
37422687
reach
"On the contrary, the anti-oncogene phosphatase and tensin homology deleted on chromosome 10 (PTEN), TSC complex subunit 1 (TSC1), and TSC complex subunit 2 (TSC2) can inhibit the progress of the mTOR pathway."
29556324
reach
"We also analyzed REDD1 (RTP801), which has been shown to be strongly induced under hypoxic conditions in a HIF-1alpha dependent manner XREF_BIBR and recent studies also suggest that REDD1 plays a role in the TSC1 and TSC2 mediated inhibition of mTOR XREF_BIBR."
19587783
reach
"Interestingly, mice with B cells that overexpress mTOR because of a TSC1 deletion (TSC1 normally inhibits mTOR, _ FIG) also demonstrate similar defects in B-cell differentiation and antibody production [XREF_BIBR]."
24565200
reach
"However, it has also been reported that TSC1 and TSC2 may function to inhibit S6K independent of mTOR (Jaeschke et al., 2002; Radimerski et al., 2002)."
14651849
reach
"As the tuberous sclerosis genes, TSC1 and TSC2, normally inhibit mTOR, the mTOR pathway is hyperactivated in TSC, promoting tumor growth and epileptogenesis, and mTOR inhibitors are a proven treatment for tumors and epilepsy in TSC."
31605778
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"TSC1 and hamartin is an upstream inhibitor of mTOR, which regulates cell growth and protein degradation [XREF_BIBR]."
28828560
sparser
"This deficit and the associated behavioral symptoms could be ascribed to the loss of inhibition of mammalian target of rapamycin (mTOR) by Tsc1."
27857688
reach
"It is now generally recognized that the primary function of the TSC1 and TSC2 protein complex is to inhibit mTOR signaling."
20412061
reach
"Recent studies also indicate that REDD1 (RTP801), induced under hypoxic conditions in a HIF-1alpha dependent manner XREF_BIBR, plays a role in the TSC1 (hamartin)/TSC2 (tuberin)-mediated inhibition of mTOR XREF_BIBR, these indicating a reciprocal regulatory control between HIF-1alpha and mTOR."
19587783
signor
"These findings strongly implicate the tuberin-hamartin tumor suppressor complex as an inhibitor of mtor. Here, we show that hamartin and tuberin function together to inhibit mammalian target of rapamycin (mtor)-mediated signaling to eukaryotic initiation factor 4e-binding protein 1 (4e-bp1) and ribosomal protein s6 kinase 1 (s6k1)."
12271141
reach
"Hamartin and tuberin, the protein products of TSC1 and TSC2, inhibit mammalian target of rapamycin (mTOR) (41)."
21289542
sparser
"In summary, we provided evidence that Tsc1 -inhibition of MTOR represses PV+/FS properties in a cohort of SST-Cre -lineage CINs."
31676823
reach
"TSC2 protein complexes with TSC1 and blocks the ability of the Rheb (Ras homolog enriched in brain) GTPase to activate mTOR signaling and thus induces autophagy [13, 14]."
31783925
reach
"This can stimulate autophagy by activating AMPK or by upregulating phosphatase and tensin homologue (PTEN, a PIP 3 3 ' phosphatase) and TSC1 which inhibits mTOR."
20188203
reach
"Interestingly, loss of either TSC1 or TSC2, which leads to hyperactive mTOR, also triggers ER stress and the UPR - indicating that hyperactive mTOR leads to the activation of PERK and generates the PA to support increased mTOR activity."
23507202
reach
"TSC1 and TSC2 negatively regulate the activity of the mammalian target of rapamycin complex 1 (mTORC1), and deletion of Tsc1 or Tsc2 from mouse oocytes in primordial and further developed follicles has been shown to cause overactivation of the entire ovarian pool and subsequent POF in early adulthood [69,70]."
31548505
reach
"Activation of mTOR by loss of the inhibitory TSC1 and TSC2 function resulted in decreased NF-kappaB activity in mouse embryonic fibroblasts (Ghosh et al., 2006)."
29768212
reach
"Gene expression analysis performed with RT2 profiler array for mTOR regulatory pathway indicated an increase in genes that encode for AMPK subunits as well as its targets such as Deptor and Tsc1, which are known to directly inhibit mTOR function."
29484131
sparser
"Canonical inhibition of mTOR by the TSC1 / TSC2 heterodimer—the TSC1 – TSC2 link is the top-ranked correlation in the entire data set, with ρ = 0.93 ( P < 10 −117 )—is reflected in the anti-correlation of fitness profiles connecting the TSC1/2 cluster and the mTOR cluster."
30979825
reach
"Tuberous sclerosis complex 1 (Tsc1) suppresses mTOR signaling, and loss of function mutations of Tsc1 cause tumors and a variety of neurological symptoms including intellectual disability, seizures, and autism."
29163060
reach
"However, mTOR is negatively regulated by complex of tuberin and hamartin [XREF_BIBR]."
21513566
reach
"However, only four were observed to be differentially regulated during the first 120 hpf : rps6ka1, mapk1 and the mTORC2 complex member rictora, all of which encode molecules that promote mTOR signaling, and tsc1a, which encodes the tumor sclerosis complex protein, hamartin that inhibits mTOR signaling."
29201571
sparser
"According to a model based on these data, in the absence of growth factors the TSC1–TSC2 complex is hypophosphorylated and inhibits mTOR."
12935885
reach
"Notably, loss of both FNIP1 and TSC1 has been shown to synergistically induce mTOR activity [49], a finding that can be explained in part by their roles as Hsp90 co-chaperones [38]."
32327294
eidos
"Although mTOR is less active during fasting , Tsc1 deficiency constitutively activated mTOR , promoted PER1 nuclear translocation , and reduced Rev-Erbalpha expression ( Fig. 6g-l ) ."
32001717