Affinage

CRTC1

CREB-regulated transcription coactivator 1 · UniProt Q6UUV9

Length
634 aa
Mass
67.3 kDa
Annotated
2026-04-28
100 papers in source corpus 20 papers cited in narrative 20 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CRTC1 is a signal-regulated transcriptional coactivator that integrates calcium and cAMP inputs to drive CREB-dependent and AP-1-dependent gene expression programs essential for synaptic plasticity, circadian entrainment, dendritic morphogenesis, and other processes. In its basal state, CRTC1 is retained in the cytoplasm by SIK-family kinase-mediated phosphorylation at Ser151; calcium influx through L-type VGCCs or NMDA receptors activates calcineurin/PP2B, which dephosphorylates CRTC1 and triggers its KPNA1-dependent nuclear import, where it binds CREB at target promoters (Per1, Bdnf, Nr4a2, autophagy genes) and recruits p300/CBP to activate transcription (PMID:19244510, PMID:20631169, PMID:25277455, PMID:30809299). SIK1 itself is a CRTC1/CREB target gene that rephosphorylates CRTC1, establishing a negative feedback loop that gates circadian phase-shifting in the suprachiasmatic nucleus and limits transcriptional responses in neurons (PMID:23993098, PMID:31672960). The CRTC1 N-terminal CREB-binding domain is recurrently hijacked in the CRTC1-MAML2 fusion oncoprotein, which constitutively activates CREB, AP-1, MYC, and downstream lncRNA (LINC00473) transcriptional programs to drive mucoepidermoid carcinoma and skin hidradenoma (PMID:15961999, PMID:19164581, PMID:25071166, PMID:29353885).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2005 High

    Establishing that the CRTC1 N-terminus directly binds CREB and that this interaction is essential for the transforming activity of the CRTC1-MAML2 fusion provided the first molecular framework for CRTC1 as a CREB coactivator and explained how the t(11;19) translocation drives mucoepidermoid carcinoma.

    Evidence Co-IP, in vitro binding, reporter assays, and dominant-negative CREB experiments in MEC-derived cells

    PMID:15961999

    Open questions at the time
    • No structural detail of the CRTC1–CREB interface
    • Wild-type CRTC1 coactivator function in normal cells not yet tested
  2. 2006 High

    Demonstrating that neuronal activity drives CRTC1 nuclear translocation and that this is required specifically for late-phase LTP (but not early LTP) established CRTC1 as a gating coactivator for transcription-dependent synaptic plasticity.

    Evidence Subcellular fractionation, live imaging, dominant-negative and shRNA experiments with LTP electrophysiology in hippocampal slices

    PMID:17183642

    Open questions at the time
    • Upstream kinase/phosphatase cascade not yet identified
    • In vivo behavioral relevance not tested
  3. 2006 High

    Showing that sustained CRTC1-MAML2 expression is required for tumor cell survival confirmed the fusion as an oncogenic driver rather than a passenger, validating it as a therapeutic target in MEC.

    Evidence RNAi knockdown with rescue by RNAi-resistant construct, colony formation and xenograft assays

    PMID:16652146

    Open questions at the time
    • Downstream effector pathways of the fusion not yet dissected
  4. 2009 High

    Identifying calcineurin-dependent dephosphorylation and calcium channel-gated nuclear import of CRTC1, together with SIK1 as a CRTC1/CREB target gene that rephosphorylates CRTC1, defined the core activation–feedback circuit controlling CRTC1 in neurons.

    Evidence Live-cell imaging, pharmacological inhibitors (calcineurin, L-type VGCC), shRNA knockdown, dendritic growth assays in cortical neurons

    PMID:19244510

    Open questions at the time
    • Specific phosphorylation sites involved not mapped in this study
    • Whether SIK1 directly phosphorylates CRTC1 in neurons or acts via intermediates not resolved
  5. 2009 High

    Discovering that CRTC1 is recruited to AP-1 target promoters and physically associates with c-Jun/c-Fos expanded CRTC1 function beyond CREB to AP-1-dependent transcription, and showed AP-1 is essential for CRTC1-MAML2-driven transformation.

    Evidence ChIP, reciprocal Co-IP, CRTC1 knockout cells, colony formation assays

    PMID:19164581

    Open questions at the time
    • Whether CRTC1 coactivates AP-1 in normal (non-oncogenic) physiology not resolved
    • Structural basis of CRTC1–AP-1 interaction unknown
  6. 2010 High

    Showing that β-amyloid suppresses CRTC1 function by reducing L-type VGCC calcium influx and blocking calcineurin-dependent Ser151 dephosphorylation, with rescue by CRTC1-S151A, identified CRTC1 dysfunction as a mechanism linking Aβ to transcriptional and memory deficits in Alzheimer's disease models.

    Evidence Phospho-specific immunoblotting, constitutively active CRTC1 mutant rescue, gene expression profiling, behavioral memory tests in APP(Sw,Ind) transgenic mice

    PMID:20631169

    Open questions at the time
    • Whether restoring CRTC1 activity rescues cognitive deficits in vivo not fully demonstrated
    • Contribution of other TORCs in AD not assessed
  7. 2010 Medium

    Identifying that LKB1 loss derepresses CRTC1 nuclear localization and CRTC1-dependent NR4A2 expression linked the LKB1-SIK-CRTC1 axis to lung cancer cell growth, extending CRTC1's oncogenic relevance beyond the fusion context.

    Evidence Immunoblotting, subcellular fractionation, siRNA knockdown of NR4A2, growth assays in LKB1-null vs. wildtype cells

    PMID:20010869

    Open questions at the time
    • Single-lab study
    • Whether CRTC1 itself is required for LKB1-null tumor growth not directly tested
  8. 2013 High

    Establishing that light-induced CRTC1 nuclear translocation in the SCN activates Per1 and Sik1, and that SIK1 feedback limits circadian phase-shifting, placed CRTC1 at the core of the photic entrainment pathway and explained behavioral gating of jet-lag recovery.

    Evidence In vivo SCN-targeted shRNA knockdown, behavioral wheel-running assays, ChIP of CRTC1 at Per1, immunohistochemistry for rhythmic CRTC1 nuclear expression

    PMID:23699513 PMID:23993098

    Open questions at the time
    • Whether CRTC1 knockout animals show circadian phenotypes not tested
    • Kinetics of CRTC1 dephosphorylation after photic stimulus not resolved
  9. 2014 High

    Region-specific in vivo knockdown showing CRTC1 is required in the basolateral amygdala but not hippocampus for fear memory, combined with ChIP at IEG promoters, established brain-region selectivity of CRTC1-dependent memory encoding.

    Evidence Lentiviral shRNA in specific brain regions, fear conditioning behavior, ChIP for CRTC1 at IEG promoters

    PMID:25277455

    Open questions at the time
    • Mechanism of region-specific CRTC1 engagement not explained
    • Whether CRTC1 is required for other amygdala-dependent behaviors not tested
  10. 2014 High

    Identifying that CRTC1-MAML2 interacts with MYC proteins and that this interaction is necessary for transformation added MYC as a third major transcription factor axis co-opted by the fusion oncoprotein.

    Evidence Co-IP, gene expression profiling, loss-of-function disrupting C1/M2-MYC interface, transformation assays in MEC cells

    PMID:25071166

    Open questions at the time
    • Whether wild-type CRTC1 interacts with MYC in normal cells not tested
    • Structural basis of CRTC1-MAML2–MYC interaction unknown
  11. 2014 High

    Showing CRTC1 is recruited to HBV cccDNA at the preS2/S promoter with CREB, and that HBx stabilizes CRTC1 protein, revealed viral exploitation of host CRTC1 coactivator activity for HBV transcription.

    Evidence ChIP on cccDNA, Co-IP, siRNA knockdown, dominant-negative CRTC1, HBsAg/pgRNA quantification

    PMID:25300488

    Open questions at the time
    • Whether targeting CRTC1 reduces HBV in vivo not tested
    • Mechanism by which HBx stabilizes CRTC1 not defined
  12. 2018 High

    Identifying LINC00473 as a CRTC1-MAML2-induced lncRNA that binds NONO to feed back and amplify CREB-dependent transcription revealed a lncRNA-mediated feed-forward loop in the fusion's oncogenic program.

    Evidence Gene expression profiling, RNAi of LINC00473, RNA pulldown/Co-IP with NONO, xenograft tumor growth assays

    PMID:29353885

    Open questions at the time
    • Whether LINC00473 has a role downstream of wild-type CRTC1 not tested
    • Structural basis of LINC00473–NONO interaction unknown
  13. 2019 Medium

    Identifying KPNA1 (Importin-α5) as the nuclear import receptor for CRTC1 provided the first mechanistic detail of how dephosphorylated CRTC1 gains nuclear access.

    Evidence Co-IP of CRTC1 with KPNA1, siRNA knockdown, immunofluorescence of CRTC1 localization, ChIP

    PMID:30809299

    Open questions at the time
    • Single-lab study
    • NLS on CRTC1 recognized by KPNA1 not mapped
    • Whether other importins contribute not tested
  14. 2019 High

    Demonstrating that SIK1 phosphorylates CRTC1 to suppress CREB-driven osteogenic gene expression, and that SIK1 KO mice have increased bone mass, extended the SIK-CRTC1 axis to bone anabolism.

    Evidence SIK1 KO mice with bone histomorphometry, kinase activity assay, reporter assays, CRTC1 phosphorylation immunoblotting

    PMID:31672960

    Open questions at the time
    • Whether bone phenotype is mediated specifically through CRTC1 vs. CRTC2/3 not resolved
  15. 2021 High

    Showing that LTD stimuli specifically dephosphorylate CRTC1-Ser151 to drive autophagy gene expression required for late-phase LTD, and that CRTC1 competes with FXR for CREB binding, expanded CRTC1 function to depression-type synaptic plasticity and autophagy.

    Evidence Phospho-Ser151 immunoblotting, live imaging, Co-IP of CRTC1/CREB/FXR, autophagy assays, electrophysiological LTD recording

    PMID:34289350

    Open questions at the time
    • In vivo behavioral consequence of CRTC1-dependent autophagy in LTD not tested
    • Mechanism of CRTC1–FXR competition not structurally characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • No high-resolution structure of the CRTC1–CREB complex exists, and the precise NLS/phosphodegron switching mechanism, the full spectrum of CRTC1-dependent transcriptional targets across tissues, and the in vivo consequences of CRTC1 genetic ablation in adult brain remain unresolved.
  • No crystal or cryo-EM structure of CRTC1 or CRTC1–CREB complex
  • Full-body Crtc1 knockout phenotype in adult conditional models not reported in timeline
  • Relative contributions of CRTC1 vs. CRTC2/CRTC3 in overlapping tissues not systematically dissected

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 9 GO:0060090 molecular adaptor activity 3
Localization
GO:0005634 nucleus 7 GO:0005829 cytosol 4
Pathway
R-HSA-74160 Gene expression (Transcription) 7 R-HSA-162582 Signal Transduction 5 R-HSA-112316 Neuronal System 4 R-HSA-1643685 Disease 3 R-HSA-9909396 Circadian clock 2 R-HSA-9612973 Autophagy 1
Partners
CREB1FXRJUNKPNA1MAML2NONOSIK1

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 The MECT1 (CRTC1) N-terminal CREB-binding domain in the MECT1-MAML2 fusion protein binds directly to CREB, recruits p300/CBP into the CREB complex through a binding domain on MAML2, and constitutively activates CREB-dependent transcription; blocking CREB DNA binding markedly reduces the transforming activity of the fusion oncogene. Co-immunoprecipitation, reporter gene assays, dominant-negative CREB experiments, in vitro binding assays The EMBO journal High 15961999
2009 CRTC1 is required for activity-dependent CREB-target gene expression and dendritic growth in developing cortical neurons; Ca2+ influx via voltage-gated calcium channels induces CRTC1 dephosphorylation and calcineurin-dependent nuclear translocation, which initiates CREB-target gene transcription including SIK1; SIK1 then promotes CRTC1 rephosphorylation as a negative feedback mechanism. Live-cell imaging of nuclear translocation, pharmacological inhibitors (calcineurin, calcium channels), dominant-negative and shRNA knockdown of CRTC1, in vivo and in vitro dendritic growth assays The Journal of neuroscience High 19244510
2006 CRTC1 (TORC1) undergoes neuronal activity-induced translocation from cytoplasm to nucleus, a process required for CRE-dependent gene expression and late-phase LTP; overexpressing dominant-negative CRTC1 suppressed L-LTP maintenance without affecting E-LTP, while wild-type CRTC1 overexpression facilitated L-LTP induction in hippocampal slices. Subcellular fractionation and live imaging of CRTC1 translocation, dominant-negative overexpression, shRNA knockdown, LTP electrophysiology in hippocampal slices, CRE-luciferase reporter assays PloS one High 17183642
2009 CRTC1 functions as an indispensable modulator of AP-1 transcription: after TPA stimulation, CRTC1 is recruited to AP-1 target gene promoters and associates with c-Jun and c-Fos; CRTC1 synergizes with c-Jun to promote cellular growth, and CRTC1-deficient cells cannot undergo AP-1-dependent proliferation. The CRTC1-MAML2 oncoprotein binds and activates both c-Jun and c-Fos, and AP-1 ablation disrupts CRTC1-MAML2-driven transformation. Chromatin immunoprecipitation, Co-IP, reporter gene assays, CRTC1 knockout cells, colony formation assays Proceedings of the National Academy of Sciences High 19164581
2010 Beta-amyloid (Abeta) suppresses CRTC1-dependent gene transcription by reducing calcium influx through L-type VGCCs, thereby disrupting PP2B/calcineurin-dependent CRTC1 dephosphorylation at Ser151; expression of constitutively active CRTC1 S151A or calcineurin mutants rescues CRTC1 transcriptional activity in APP(Sw,Ind) neurons, and CRTC1-dependent memory genes (Bdnf, c-fos, Nr4a2) are selectively reduced. Phospho-specific immunoblotting, pharmacological channel blockers/agonists, dominant-negative and constitutively active CRTC1 mutants, gene expression profiling, behavioral memory tests in transgenic mice The Journal of neuroscience High 20631169
2010 CRTC1 nuclear localization is enhanced in LKB1-null lung cancer cells; somatic loss of LKB1 is associated with underphosphorylation of endogenous CRTC1 and increased expression of the CRTC1 target gene NR4A2/Nurr1; inhibition of NR4A2 suppresses growth of LKB1-null but not LKB1-wildtype tumors. Immunoblotting for CRTC1 phosphorylation status, subcellular fractionation/immunofluorescence, siRNA knockdown of NR4A2, growth assays in LKB1-null vs wildtype cells Oncogene Medium 20010869
2010 BDNF-induced dendritic growth requires a functional CREB-CRTC1 interaction; NMDA receptor activation by glutamate drives CRTC1 nuclear translocation via calcineurin, and this translocation is essential for BDNF's effects on dendritic length and complexity. shRNA knockdown of CRTC1 abolishes BDNF-induced dendritic growth of cortical neurons. Dominant-negative CREB mutant (unable to bind CRTC1), shRNA knockdown of CRTC1, live-cell imaging, pharmacological NMDA receptor blockade, dendritic morphology analysis The Journal of biological chemistry High 20639200
2013 In the suprachiasmatic nucleus (SCN), a photic entrainment stimulus causes CRTC1 to coactivate CREB, inducing expression of Per1 and Sik1; SIK1 then phosphorylates and deactivates CRTC1, providing negative feedback that limits further clock shifts. Knockdown of Sik1 in the SCN results in increased behavioral phase shifts and rapid re-entrainment after jet lag. In vivo SCN-targeted knockdown (lentiviral shRNA), behavioral wheel-running assays, immunofluorescence for CRTC1 nuclear localization, gene expression analysis (Per1, Sik1) Cell High 23993098
2013 In the SCN, CRTC1 shows rhythmic nuclear expression peaking at mid-subjective day, and light pulses during early and late subjective night induce strong nuclear accumulation of CRTC1 specifically (CRTC2 is unaffected by light). ChIP analysis confirmed CRTC1 association with CREB at the Period1 gene 5' regulatory region; CRTC1 overexpression markedly upregulates Period1 transcription. Immunohistochemistry with subcellular localization scoring, chromatin immunoprecipitation (ChIP), CRE-luciferase reporter assays, immunofluorescence The Journal of neuroscience High 23699513
2014 CRTC1 nuclear translocation is controlled by convergent constitutive kinase pathways and the activity-regulated phosphatase calcineurin; nuclear CRTC1 triggers activity-dependent association with CREB at IEG promoters. During contextual fear conditioning, endogenous CRTC1 nuclear recruitment occurs in the basolateral amygdala but not hippocampus; CRTC1 knockdown in amygdala (not hippocampus) attenuates fear memory. Constitutively nuclear CRTC1 lentiviral expression, shRNA knockdown in specific brain regions, in vivo fear conditioning behavioral assay, ChIP for CRTC1 at IEG promoters, live-cell imaging of CRTC1 translocation Neuron High 25277455
2006 Sustained expression of MECT1-MAML2 (CRTC1-MAML2) is required for tumor cell growth in MEC salivary gland cancer cells carrying the t(11;19) translocation; RNAi-mediated knockdown of the fusion peptide caused ≥90% colony growth inhibition in MEC lines, which was rescued by a mutant MAML2 construct resistant to RNAi. RNAi hairpin knockdown, colony formation assay, in vivo xenograft assay in nude mice, rescue experiment with RNAi-resistant construct Oncogene High 16652146
2014 CRTC1-MAML2 fusion oncoprotein interacts with MYC proteins and activates MYC transcription targets including genes involved in cell growth, metabolism, and survival; the CRTC1-MAML2–MYC interaction is necessary for CRTC1-MAML2-driven cell transformation. Co-immunoprecipitation, gene expression profiling, loss-of-function experiments disrupting the C1/M2-MYC interface, transformation assay in human MEC cells Proceedings of the National Academy of Sciences High 25071166
2018 CRTC1-MAML2 induces transcription of lncRNA LINC00473, which is dependent on CRTC1-MAML2's ability to activate CREB-mediated transcription; LINC00473 in turn binds NONO (a cAMP signaling component) to enhance CRTC1-MAML2-driven CREB-mediated transcription, forming a feed-forward loop essential for MEC cell growth. Gene expression profiling after CRTC1-MAML2 depletion, RNAi knockdown of LINC00473, xenograft tumor growth assays, RNA pulldown/Co-IP of LINC00473 with NONO, RNA-ISH for subcellular localization Oncogene High 29353885
2014 CRTC1 is required for HBV transcription and replication; CRTC1 interacts with CREB and they are mutually required for recruitment to the preS2/S promoter on cccDNA. HBV transactivator HBx stabilizes CRTC1 protein and promotes its transcriptional activity on HBV. Co-immunoprecipitation, ChIP on cccDNA, dominant-negative CRTC1, ectopic overexpression, siRNA knockdown, HBsAg/pgRNA/cccDNA level measurement Nucleic acids research High 25300488
2019 SIK1 phosphorylates CRTC1, preventing CRTC1 from enhancing CREB transcriptional activity for osteogenic gene expression (including Id1); SIK1 knockdown in preosteoblasts increased osteoblast differentiation, and SIK1 KO mice show higher bone mass. BMP2 suppresses SIK1 expression and activity via PKA-dependent mechanisms to stimulate osteogenesis. Gene knockdown (siRNA for SIK1/2/3), SIK1 KO mice with bone histomorphometry, kinase activity assay, reporter gene assay for CREB/CRTC1 activity, Western blotting for CRTC1 phosphorylation Cell death & disease High 31672960
2019 CRTC1 nuclear import is mediated by the importin KPNA1 (Importin-α5), which escorts CRTC1 as cargo across the nuclear envelope; DACE blocks CRTC1 nuclear import, thereby inhibiting CREB/CRTC1-driven SOX10 induction and MITF-M transcription to suppress melanogenesis. Co-immunoprecipitation of CRTC1 with KPNA1, siRNA knockdown, immunofluorescence of CRTC1 nuclear localization, chromatin immunoprecipitation, RT-PCR Theranostics Medium 30809299
2021 LTD-inducing stimuli specifically dephosphorylate CRTC1 at Ser-151 and recruit CRTC1 from cytoplasm to nucleus, where it competes with FXR for binding to CREB and drives autophagy gene expression required for NMDAR-dependent late-phase LTD; disrupting CREB-CRTC1 synergistic actions impairs transcription-dependent autophagy and prevents L-LTD. Phospho-specific immunoblotting for CRTC1 Ser-151, live-cell imaging of CRTC1 nuclear translocation, dominant-negative constructs, Co-IP of CRTC1/CREB/FXR, autophagy assays, electrophysiological LTD recording Cell reports High 34289350
2014 Excitatory GABA-induced BDNF transcription via promoter IV requires the combination of nuclear-localized CRTC1 (via calcineurin pathway) and CREB phosphorylation; CRTC1 nuclear translocation in cortical neurons is specifically induced by GABA via Ca2+/calcineurin signaling. Dominant-negative CREB overexpression, CRTC1 nuclear translocation imaging, pharmacological inhibitors (calcineurin, CaMK, MAPK), Bdnf-promoter IV-luciferase reporter, mRNA quantification Journal of neurochemistry Medium 24965890
2007 The CRTC1-MAML2 gene fusion is found in benign hidradenomas of the skin (50% of cases), all of which show clear cell morphology, indicating the fusion oncogene has transforming activity beyond salivary gland tumors and is associated with clear cell differentiation across exocrine glands. FISH (CRTC1 and MAML2 loci), RT-PCR for fusion transcript, immunohistochemistry for fusion protein expression in tumor cells Genes, chromosomes & cancer Medium 17334997
2022 miR-184-3p directly targets CRTC1 mRNA 3'UTR; reduced miR-184-3p leads to CRTC1 upregulation in β-cells, which protects against lipotoxicity- and inflammation-induced apoptosis; silencing CRTC1 abrogates the protective effect of miR-184-3p inhibition. NKX6.1 directly controls miR-184 expression via its DNA-binding sites in the MIR184 promoter. miR-184-3p mimic/inhibitor experiments, siRNA knockdown of CRTC1, chromatin immunoprecipitation for NKX6.1 at MIR184 promoter, apoptosis assays, mRNA/protein quantification Cell death discovery Medium 35906204

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Effective and selective targeting of leukemia cells using a TORC1/2 kinase inhibitor. Nature medicine 299 20072130
2010 A reappraisal of the MECT1/MAML2 translocation in salivary mucoepidermoid carcinomas. The American journal of surgical pathology 209 20588178
2013 The CRTC1-SIK1 pathway regulates entrainment of the circadian clock. Cell 174 23993098
2016 Splicing factor 1 modulates dietary restriction and TORC1 pathway longevity in C. elegans. Nature 162 27919065
2009 Nutrient control of TORC1, a cell-cycle regulator. Trends in cell biology 155 19419870
2006 TSC1/TSC2 and Rheb have different effects on TORC1 and TORC2 activity. Proceedings of the National Academy of Sciences of the United States of America 148 16627617
2017 Regulation of Autophagy through TORC1 and mTORC1. Biomolecules 122 28686223
2005 Transforming activity of MECT1-MAML2 fusion oncoprotein is mediated by constitutive CREB activation. The EMBO journal 121 15961999
2009 Sfp1 interaction with TORC1 and Mrs6 reveals feedback regulation on TOR signaling. Molecular cell 119 19328065
2009 TORC1 regulates activity-dependent CREB-target gene transcription and dendritic growth of developing cortical neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 111 19244510
2014 State transitions in the TORC1 signaling pathway and information processing in Saccharomyces cerevisiae. Genetics 104 25085507
2010 beta-Amyloid disrupts activity-dependent gene transcription required for memory through the CREB coactivator CRTC1. The Journal of neuroscience : the official journal of the Society for Neuroscience 103 20631169
2004 A study of MECT1-MAML2 in mucoepidermoid carcinoma and Warthin's tumor of salivary glands. The Journal of molecular diagnostics : JMD 103 15269296
2019 Neuronal TORC1 modulates longevity via AMPK and cell nonautonomous regulation of mitochondrial dynamics in C. elegans. eLife 97 31411562
2018 Spatially Distinct Pools of TORC1 Balance Protein Homeostasis. Molecular cell 93 30527664
2006 Requirement of TORC1 for late-phase long-term potentiation in the hippocampus. PloS one 93 17183642
2010 TOR signaling never gets old: aging, longevity and TORC1 activity. Ageing research reviews 92 20385253
2017 RNA polymerase III limits longevity downstream of TORC1. Nature 91 29186112
2017 TORC1 organized in inhibited domains (TOROIDs) regulate TORC1 activity. Nature 87 28976958
2013 TORC1-regulated protein kinase Npr1 phosphorylates Orm to stimulate complex sphingolipid synthesis. Molecular biology of the cell 86 23363605
2014 Region-specific activation of CRTC1-CREB signaling mediates long-term fear memory. Neuron 83 25277455
2007 Frequent fusion of the CRTC1 and MAML2 genes in clear cell variants of cutaneous hidradenomas. Genes, chromosomes & cancer 82 17334997
2015 TORC1 promotes phosphorylation of ribosomal protein S6 via the AGC kinase Ypk3 in Saccharomyces cerevisiae. PloS one 80 25767889
2019 Multilayered Control of Protein Turnover by TORC1 and Atg1. Cell reports 76 31553916
2016 Sestrin regulation of TORC1: Is Sestrin a leucine sensor? Science signaling 76 27273098
2008 t(11;19) translocation and CRTC1-MAML2 fusion oncogene in mucoepidermoid carcinoma. Oral oncology 76 18486532
2015 TORC1 and TORC2 work together to regulate ribosomal protein S6 phosphorylation in Saccharomyces cerevisiae. Molecular biology of the cell 73 26582391
2011 WIPI1 coordinates melanogenic gene transcription and melanosome formation via TORC1 inhibition. The Journal of biological chemistry 72 21317285
2010 Regulation of dendritic development by BDNF requires activation of CRTC1 by glutamate. The Journal of biological chemistry 71 20639200
2015 Nitrogen regulates AMPK to control TORC1 signaling. Current biology : CB 68 25639242
2018 The TORC1-Regulated CPA Complex Rewires an RNA Processing Network to Drive Autophagy and Metabolic Reprogramming. Cell metabolism 66 29606597
2016 Conserved regulators of Rag GTPases orchestrate amino acid-dependent TORC1 signaling. Cell discovery 65 27462445
2006 Sustained expression of Mect1-Maml2 is essential for tumor cell growth in salivary gland cancers carrying the t(11;19) translocation. Oncogene 65 16652146
2018 Cutaneous Melanocytoma With CRTC1-TRIM11 Fusion: Report of 5 Cases Resembling Clear Cell Sarcoma. The American journal of surgical pathology 64 29240581
2014 Molecular architecture and function of the SEA complex, a modulator of the TORC1 pathway. Molecular & cellular proteomics : MCP 64 25073740
2020 TORC1 inactivation stimulates autophagy of nucleoporin and nuclear pore complexes. The Journal of cell biology 62 32453403
2021 A TORC1-histone axis regulates chromatin organisation and non-canonical induction of autophagy to ameliorate ageing. eLife 61 33988501
2017 Correlation of Crtc1/3-Maml2 fusion status, grade and survival in mucoepidermoid carcinoma. Oral oncology 61 28438292
2014 Reciprocal conversion of Gtr1 and Gtr2 nucleotide-binding states by Npr2-Npr3 inactivates TORC1 and induces autophagy. Autophagy 61 25046117
2012 microRNA-21 governs TORC1 activation in renal cancer cell proliferation and invasion. PloS one 61 22685542
2014 The TORC1 effector kinase Npr1 fine tunes the inherent activity of the Mep2 ammonium transport protein. Nature communications 59 24476960
2015 SEA you later alli-GATOR--a dynamic regulator of the TORC1 stress response pathway. Journal of cell science 57 25934700
2014 TORC1 regulators Iml1/GATOR1 and GATOR2 control meiotic entry and oocyte development in Drosophila. Proceedings of the National Academy of Sciences of the United States of America 54 25512509
2012 The Vam6 and Gtr1-Gtr2 pathway activates TORC1 in response to amino acids in fission yeast. Journal of cell science 54 22344254
2009 The coactivator CRTC1 promotes cell proliferation and transformation via AP-1. Proceedings of the National Academy of Sciences of the United States of America 54 19164581
2018 Gtr/Ego-independent TORC1 activation is achieved through a glutamine-sensitive interaction with Pib2 on the vacuolar membrane. PLoS genetics 53 29698392
2019 Phosphorus Availability Regulates TORC1 Signaling via LST8 in Chlamydomonas. The Plant cell 51 31712405
2020 Insulin/IGF signaling and TORC1 promote vitellogenesis via inducing juvenile hormone biosynthesis in the American cockroach. Development (Cambridge, England) 49 33097549
2015 Branched-Chain Aminotransferases Control TORC1 Signaling in Saccharomyces cerevisiae. PLoS genetics 49 26659116
2018 CRTC1-MAML2 fusion-induced lncRNA LINC00473 expression maintains the growth and survival of human mucoepidermoid carcinoma cells. Oncogene 45 29353885
2013 Clock and light regulation of the CREB coactivator CRTC1 in the suprachiasmatic circadian clock. The Journal of neuroscience : the official journal of the Society for Neuroscience 43 23699513
2021 Indole-3-acetic acid is a physiological inhibitor of TORC1 in yeast. PLoS genetics 42 33690632
2022 Cutaneous Melanocytic Tumor With CRTC1::TRIM11 Translocation : An Emerging Entity Analyzed in a Series of 41 Cases. The American journal of surgical pathology 40 35993578
2015 Evolutionary conservation of TORC1 components, TOR, Raptor, and LST8, between rice and yeast. Molecular genetics and genomics : MGG 40 25956502
2009 Enhanced activity of the CREB co-activator Crtc1 in LKB1 null lung cancer. Oncogene 40 20010869
2023 Snf1/AMPK fine-tunes TORC1 signaling in response to glucose starvation. eLife 38 36749016
2013 CRTC1-MAML2 and CRTC3-MAML2 fusions were not detected in metaplastic Warthin tumor and metaplastic pleomorphic adenoma of salivary glands. The American journal of surgical pathology 37 24121173
2021 Conserved and Divergent Mechanisms That Control TORC1 in Yeasts and Mammals. Genes 36 33445779
2021 Neuronal activity recruits the CRTC1/CREB axis to drive transcription-dependent autophagy for maintaining late-phase LTD. Cell reports 36 34289350
2017 Pib2 and the EGO complex are both required for activation of TORC1. Journal of cell science 36 28993463
2020 TORC1 Determines Fab1 Lipid Kinase Function at Signaling Endosomes and Vacuoles. Current biology : CB 35 33157024
2017 TORC1-dependent sumoylation of Rpc82 promotes RNA polymerase III assembly and activity. Proceedings of the National Academy of Sciences of the United States of America 35 28096404
2018 The TORC1-Sch9 pathway as a crucial mediator of chronological lifespan in the yeast Saccharomyces cerevisiae. FEMS yeast research 34 29788208
2014 Excitatory GABA induces BDNF transcription via CRTC1 and phosphorylated CREB-related pathways in immature cortical cells. Journal of neurochemistry 31 24965890
2021 A glutamine sensor that directly activates TORC1. Communications biology 30 34535752
2014 CRTC1/MAML2 gain-of-function interactions with MYC create a gene signature predictive of cancers with CREB-MYC involvement. Proceedings of the National Academy of Sciences of the United States of America 30 25071166
2021 Phosphoproteomic responses of TORC1 target kinases reveal discrete and convergent mechanisms that orchestrate the quiescence program in yeast. Cell reports 29 34965436
2022 Manganese is a physiologically relevant TORC1 activator in yeast and mammals. eLife 28 35904415
2017 Vacuole-mediated selective regulation of TORC1-Sch9 signaling following oxidative stress. Molecular biology of the cell 28 29237820
2016 Regulation of the NR2B-CREB-CRTC1 Signaling Pathway Contributes to Circadian Pain in Murine Model of Chronic Constriction Injury. Anesthesia and analgesia 28 26440419
2008 Genome-wide expression analysis reveals TORC1-dependent and -independent functions of Sch9. FEMS yeast research 28 18759743
2021 Salivary mucoepidermoid carcinoma: histological variants, grading systems, CRTC1/3-MAML2 fusions, and clinicopathological features. Histopathology 27 34657306
2021 Fluoride Stimulates Anxiety- and Depression-like Behaviors Associated with SIK2-CRTC1 Signaling Dysfunction. Journal of agricultural and food chemistry 27 34735150
2019 Salt-inducible kinase 1 regulates bone anabolism via the CRTC1-CREB-Id1 axis. Cell death & disease 26 31672960
2017 Prenatal Mechanistic Target of Rapamycin Complex 1 (m TORC1) Inhibition by Rapamycin Treatment of Pregnant Mice Causes Intrauterine Growth Restriction and Alters Postnatal Cardiac Growth, Morphology, and Function. Journal of the American Heart Association 26 28778941
2014 Delineating the mTOR kinase pathway using a dual TORC1/2 inhibitor, AZD8055, in multiple myeloma. Molecular cancer therapeutics 26 25172964
2013 TORC1 and class I HDAC inhibitors synergize to suppress mature B cell neoplasms. Molecular oncology 25 24429254
2014 Requirement of CRTC1 coactivator for hepatitis B virus transcription. Nucleic acids research 24 25300488
2023 ARSK1 activates TORC1 signaling to adjust growth to phosphate availability in Arabidopsis. Current biology : CB 22 36963384
2021 Drosophila Activin signaling promotes muscle growth through InR/TORC1-dependent and -independent processes. Development (Cambridge, England) 22 33234715
2021 The tip of the iceberg: emerging roles of TORC1, and its regulatory functions in plant cells. Journal of experimental botany 22 33462577
2019 Nuclear Entry of CRTC1 as Druggable Target of Acquired Pigmentary Disorder. Theranostics 22 30809299
2011 Bidirectional regulation between TORC1 and autophagy in Saccharomyces cerevisiae. Autophagy 22 21490424
2021 Dermal melanocytic tumor with CRTC1-TRIM11 fusion: Report of two additional cases with review of the literature of an emerging entity. Journal of cutaneous pathology 21 33586183
2017 TORC1-mediated sensing of chaperone activity alters glucose metabolism and extends lifespan. Aging cell 21 28613034
2023 The TORC1 activates Rpd3L complex to deacetylate Ino80 and H2A.Z and repress autophagy. Science advances 20 36888706
2022 Localization of a TORC1-eIF4F translation complex during CD8+ T cell activation drives divergent cell fate. Molecular cell 20 35597236
2022 Reduced miR-184-3p expression protects pancreatic β-cells from lipotoxic and proinflammatory apoptosis in type 2 diabetes via CRTC1 upregulation. Cell death discovery 20 35906204
2021 Pib2 as an Emerging Master Regulator of Yeast TORC1. Biomolecules 20 34680122
2019 Eisosomes at the intersection of TORC1 and TORC2 regulation. Traffic (Copenhagen, Denmark) 20 31038844
2022 TORC1 and PKA activity towards ribosome biogenesis oscillates in synchrony with the budding yeast cell cycle. Journal of cell science 19 35975715
2019 Sphingolipid/Pkh1/2-TORC1/Sch9 Signaling Regulates Ribosome Biogenesis in Tunicamycin-Induced Stress Response in Yeast. Genetics 19 30824472
2019 Import of extracellular ATP in yeast and man modulates AMPK and TORC1 signalling. Journal of cell science 18 30814334
2022 V-ATPase/TORC1-mediated ATFS-1 translation directs mitochondrial UPR activation in C. elegans. The Journal of cell biology 17 36314986
2019 (Epi)genetic regulation of CRTC1 in human eating behaviour and fat distribution. EBioMedicine 17 31153815
2018 Multilayered regulation of TORC1-body formation in budding yeast. Molecular biology of the cell 17 30485160
2019 TORC1, Tel1/Mec1, and Mpk1 regulate autophagy induction after DNA damage in budding yeast. Cellular signalling 15 31201849
2018 Cdc14 Phosphatase Promotes TORC1-Regulated Autophagy in Yeast. Journal of molecular biology 15 29694832
2018 Indirect monitoring of TORC1 signalling pathway reveals molecular diversity among different yeast strains. Yeast (Chichester, England) 15 30094872
2018 The TORC1 signaling pathway regulates respiration-induced mitophagy in yeast. Biochemical and biophysical research communications 14 29787763