Affinage

CRTC1

CREB-regulated transcription coactivator 1 · UniProt Q6UUV9

Length
634 aa
Mass
67.3 kDa
Annotated
2026-06-09
100 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CRTC1 is a calcium- and cAMP-responsive transcriptional coactivator for CREB that converts neuronal and hormonal signals into activity-dependent gene programs (PMID:19244510, PMID:29269871). In the resting state it is held in the cytoplasm by phosphorylation at Ser151 by SIK-family kinases, and Ca2+ influx through L-type voltage-gated calcium channels triggers calcineurin (PP2B)-dependent dephosphorylation, nuclear translocation, and activity-dependent binding to constitutively promoter-bound CREB, where CRTC1 is selectively recruited to CRE/TATA-containing promoters to induce immediate-early and effector genes such as c-fos, Nr4a1-3, Dusp1, Ptgs2, Per1 and Bdnf (PMID:19244510, PMID:20631169, PMID:29269871). The coactivator is embedded in a self-limiting circuit: among its induced targets is SIK1, which re-phosphorylates CRTC1 to deplete it from the nucleus and terminate transcription (PMID:19244510, PMID:23993098). Through this switch CRTC1 governs circadian clock entrainment in the suprachiasmatic nucleus via light-induced Per1 induction (PMID:23993098, PMID:23699513), drives dendritic growth and associative/fear memory consolidation in cortical, hippocampal and amygdalar neurons (PMID:19244510, PMID:25277455, PMID:27587263), and supports SIK1-regulated osteoblast differentiation and the calcineurin-MITF melanogenic program (PMID:31672960, PMID:35649693). CRTC1 signaling is corrupted in disease: amyloid-beta blunts L-VGCC/calcineurin-driven CRTC1 dephosphorylation to suppress memory genes in Alzheimer's models, and restoring CRTC1 reverses these transcriptional and behavioral deficits (PMID:20631169, PMID:24760838, PMID:27587263). The t(11;19) translocation fuses the N-terminal CREB-binding domain of CRTC1 to MAML2, generating a constitutively active coactivator that recruits p300/CBP to CREB and is the principal oncogenic driver of mucoepidermoid carcinoma, producing fully penetrant salivary gland tumors in mice (PMID:15961999, PMID:16103063, PMID:33830080); the fusion's CREB-binding domain is strictly required for transformation (PMID:16103063, PMID:16652146), and it additionally co-opts AP-1 (c-Jun/c-Fos), MYC, LINC00473/NONO, and PGC-1α/PPARγ-IGF-1 and AREG/EGFR circuits to sustain tumor growth (PMID:19164581, PMID:25071166, PMID:29353885, PMID:33830080, PMID:33626346).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2005 High

    Established that the CRTC1-MAML2 fusion transforms cells by acting as a constitutive CREB coactivator, defining the oncogenic mechanism and CRTC1's intrinsic CREB-binding function.

    Evidence Co-IP, reporter assays and dominant-negative CREB rescue plus deletion mutagenesis in RK3E transformation assays

    PMID:15961999 PMID:16103063

    Open questions at the time
    • Did not define the endogenous regulatory inputs controlling wild-type CRTC1
    • Structural basis of CRTC1 CREB-binding domain interaction not resolved
  2. 2006 High

    Showed the fusion is continuously required for tumor maintenance, not merely initiation, validating it as a therapeutic dependency.

    Evidence shRNA knockdown with RNAi-resistant rescue in t(11;19) MEC lines and nude mouse xenografts

    PMID:16652146

    Open questions at the time
    • Did not identify downstream effector genes responsible for growth dependency
  3. 2009 High

    Defined the physiological activation switch: Ca2+/calcineurin-dependent dephosphorylation drives nuclear CRTC1 to support CREB-target genes and dendritic growth, with SIK1 forming a negative feedback loop.

    Evidence Live imaging, calcineurin/VGCC pharmacology, dominant-negative and siRNA in cortical neurons

    PMID:19244510

    Open questions at the time
    • Identity of the constitutive kinase(s) maintaining basal Ser151 phosphorylation not fully resolved
    • Did not establish promoter selectivity rules
  4. 2009 High

    Extended CRTC1's partner repertoire beyond CREB to AP-1, showing physical association with c-Jun/c-Fos drives both normal proliferation and fusion-driven transformation.

    Evidence ChIP, Co-IP, dominant-negative AP-1 and colony formation assays

    PMID:19164581

    Open questions at the time
    • Mechanism of CRTC1 recruitment to AP-1 promoters not defined
    • Relative contribution of CREB vs AP-1 in transformation unquantified
  5. 2009 Medium

    Placed CRTC1 downstream of the LKB1 tumor suppressor, where LKB1 loss underphosphorylates CRTC1 and elevates the NR4A2 target to support tumor growth.

    Evidence Phospho-CRTC1 Western blot, immunofluorescence and NR4A2 siRNA in LKB1-null lung cancer cells

    PMID:20010869

    Open questions at the time
    • Did not establish whether SIK-family kinases mediate the LKB1-CRTC1 link directly
    • Single-lab, two-approach support
  6. 2010 High

    Linked CRTC1 dysfunction to disease by showing amyloid-beta suppresses CRTC1 transcription via reduced L-VGCC Ca2+ influx and impaired Ser151 dephosphorylation, with S151A rescue.

    Evidence Phosphosite mutant rescue, L-VGCC pharmacology and behavior in APP transgenic mice

    PMID:20631169

    Open questions at the time
    • Did not establish causality between specific target genes and memory rescue
  7. 2013 High

    Demonstrated CRTC1's role in circadian entrainment, where light-driven CRTC1-CREB induction of Per1 and SIK1 creates feedback limiting phase shifts in the SCN.

    Evidence SCN transcriptomics, in vivo Sik1 knockdown, ChIP at Per1, and behavioral phase-shift/jet-lag assays

    PMID:23699513 PMID:23993098

    Open questions at the time
    • CRTC1-specific (vs CRTC2) requirement for entrainment not tested by loss-of-function
    • Per1 ChIP shows occupancy but not direct functional necessity
  8. 2014 High

    Mapped region-specific behavioral roles, showing CRTC1 nuclear recruitment in the amygdala (not hippocampus) is required for fear memory, and AAV-CRTC1 rescues Alzheimer-model deficits.

    Evidence Region-specific viral knockdown, ChIP, AAV rescue and fear/water-maze behavior in mouse models

    PMID:24760838 PMID:25277455

    Open questions at the time
    • Basis of brain-region-specific CRTC1 activation not explained
    • Which target-gene subset mediates rescue incompletely defined
  9. 2014 Medium

    Identified MYC as a new fusion partner, with the CRTC1-MAML2-MYC interaction required for transformation, broadening the oncogenic transcriptional output.

    Evidence Co-IP, reporter and gene expression profiling with transformation assays in human MEC cells

    PMID:25071166

    Open questions at the time
    • Direct vs indirect nature of the MYC interaction not resolved
    • Single lab
  10. 2015 High

    Established CRTC1 as an effector of PGE2/EP receptor signaling in colon cancer, where calcineurin/PKA-driven dephosphorylation activates proliferative and inflammatory target genes.

    Evidence Receptor antagonist/PKA/calcineurin pharmacology, loss/gain-of-function and xenografts

    PMID:26300003

    Open questions at the time
    • Relative requirement of AP-1 vs CREB partners for each target gene not dissected
  11. 2016 High

    Refined the learning-specificity of CRTC1, showing context-association (not stimuli alone) triggers Ser151 dephosphorylation and nuclear translocation driving IEGs, with gene therapy rescuing degeneration.

    Evidence One-trial fear conditioning, phospho-assays, ChIP, AAV gene therapy in presenilin cDKO mice

    PMID:27587263

    Open questions at the time
    • Upstream signal distinguishing association from single stimuli unknown
  12. 2017 Medium

    Defined the promoter-selectivity rule: activity-dependent CRTC1 recruitment occurs specifically at CRE/TATA promoters while CREB is constitutively bound, explaining gene-selective induction.

    Evidence ChIP across CRE/TATA vs CRE/TATA-less promoters with phospho and reporter assays in stimulated neurons

    PMID:29269871

    Open questions at the time
    • Mechanism by which TATA element confers CRTC1 dependence unresolved
    • Single lab
  13. 2018 Medium

    Identified LINC00473/NONO as a downstream effector and feed-forward amplifier of fusion-driven CREB transcription required for MEC survival.

    Evidence shRNA knockdown, xenografts, RNA-IP for NONO and expression profiling

    PMID:29353885

    Open questions at the time
    • Mechanism of LINC00473-NONO enhancement of CREB transcription not fully defined
  14. 2019 High

    Confirmed direct SIK1-CRTC1 regulation in a non-neural context, where SIK1 phosphorylation of CRTC1 restrains CREB-driven osteogenic genes like Id1.

    Evidence SIK1 kinase assay, SIK1 knockout mice, osteoblast differentiation and PKA inhibitor studies

    PMID:31672960

    Open questions at the time
    • Whether Ser151 is the relevant SIK1 site in osteoblasts not specified
  15. 2021 High

    Consolidated CRTC1-MAML2 as the major MEC driver and revealed actionable AREG/EGFR, PGC-1α4/PPARγ-IGF-1 circuits enabling combination therapy.

    Evidence Conditional transgenic mouse, inducible knockdown, drug screens and combination treatment in vitro/in vivo

    PMID:33626346 PMID:33830080

    Open questions at the time
    • PGC-1α4/IGF-1 arm is Medium-confidence single-lab
    • Direct vs indirect target relationships not fully mapped
  16. 2021 Medium

    Uncovered a transcription-coupled autophagy role, where NMDAR-driven CRTC1 competes with FXR for CREB to induce autophagy genes needed for late-phase LTD.

    Evidence Co-IP competition, phospho-assays, shRNA and LTD electrophysiology

    PMID:34289350

    Open questions at the time
    • Structural basis of CRTC1/FXR competition not resolved
    • Single lab
  17. 2022 Medium

    Extended the Ca2+/calcineurin-CRTC1 axis to melanogenesis (VDAC1->Ca2+->MITF) and to beta-cell survival via miR-184-3p targeting of CRTC1 mRNA.

    Evidence VDAC1 knockdown/KO, Ca2+ imaging, calcineurin assays, miRNA target validation and apoptosis assays

    PMID:35649693 PMID:35906204

    Open questions at the time
    • Direct MITF promoter occupancy by CRTC1 not shown
    • miR-184-3p/CRTC1 protective targets in beta-cells not enumerated

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis of CRTC1 promoter selectivity, the full set of kinases setting basal phosphorylation, and how cell-type context dictates which target programs CRTC1 activates remain unresolved.
  • No structural model of CRTC1-CREB-CRE/TATA assembly
  • Determinants of tissue-specific target selection unknown
  • Mechanism linking distinct upstream signals to common CRTC1 dephosphorylation undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 4 GO:0003723 RNA binding 2
Localization
GO:0005634 nucleus 5 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-112316 Neuronal System 2 R-HSA-9909396 Circadian clock 2 R-HSA-9612973 Autophagy 1
Partners
CREBCREBBP/EP300FOSJUNMAML2MYCNONOSIK1
Complex memberships
CRTC1-CREB coactivator complex

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 The MECT1-MAML2 (CRTC1-MAML2) fusion protein binds to CREB via the N-terminal CREB-binding domain of MECT1/CRTC1, recruits p300/CBP into the CREB complex through a binding domain on MAML2, and constitutively activates CREB-dependent transcription. Blocking CREB DNA binding markedly reduced the transforming activity of the fusion protein. Co-immunoprecipitation, reporter gene assays, dominant-negative CREB mutants, gene expression profiling The EMBO journal High 15961999
2005 Small in-frame deletions within the CREB-binding domain of MECT1/CRTC1 completely abolished the transforming activity of the Mect1-Maml2 fusion oncogene in RK3E epithelial cells, establishing that CRTC1's CREB-binding domain is essential for oncogenic function. The fusion activates known cAMP/CREB-regulated genes but does not alter Notch-regulated target genes. Deletion mutagenesis, RK3E transformation assay, doxycycline-inducible expression system, microarray gene expression profiling, RT-PCR validation Cancer research High 16103063
2009 CRTC1 (TORC1) is required for activity-dependent CREB-target gene expression and dendritic growth in developing cortical neurons. Ca2+ influx via voltage-gated calcium channels induced CRTC1 dephosphorylation and nuclear translocation in a calcineurin-dependent manner. Nuclear CRTC1 initiated CREB-target gene expression including SIK1, which then phosphorylated CRTC1 to deplete it from the nucleus—a negative feedback loop limiting persistent CREB/CRTC1 transcription. Live-cell imaging, pharmacological inhibitors (calcineurin inhibitor FK506, L-type VGCC blockers), dominant-negative CRTC1, siRNA knockdown, immunofluorescence, in vivo overexpression The Journal of neuroscience High 19244510
2009 CRTC1 promotes cell proliferation and transformation via AP-1. After TPA stimulation, CRTC1 is recruited to AP-1 target gene promoters and physically associates with c-Jun and c-Fos to activate transcription. The CRTC1-MAML2 oncoprotein also binds and activates both c-Jun and c-Fos; ablation of AP-1 function disrupts cellular transformation and proliferation mediated by CRTC1-MAML2. Chromatin immunoprecipitation, co-immunoprecipitation, siRNA knockdown, dominant-negative AP-1, reporter assays, colony formation assay Proceedings of the National Academy of Sciences of the United States of America High 19164581
2009 Loss of LKB1 in lung cancer cells is associated with underphosphorylation of endogenous CRTC1 and enhanced CRTC1 nuclear localization, leading to elevated expression of the CRTC1 target gene NR4A2/Nurr1. Inhibition of NR4A2 suppressed growth of LKB1-null tumors, placing CRTC1 downstream of the LKB1 tumor-suppressor pathway. Western blotting (phospho-CRTC1), immunofluorescence (nuclear localization), siRNA knockdown of NR4A2, colony formation assay Oncogene Medium 20010869
2010 Beta-amyloid suppresses CRTC1-dependent gene transcription in Alzheimer's disease model neurons by reducing calcium influx through L-type voltage-gated calcium channels, thereby disrupting PP2B/calcineurin-dependent dephosphorylation of CRTC1 at Ser151. Expression of constitutively active CRTC1 S151A or calcineurin mutants reversed transcriptional deficits. CRTC1-dependent memory genes (Bdnf, c-fos, Nr4a2) were selectively reduced coinciding with spatial memory deficits. Pharmacological manipulation (L-VGCC agonists/antagonists, NMDA/AMPA receptor blockers), phosphorylation assays, luciferase reporter, immunofluorescence, transgenic APP mouse model, behavioral testing The Journal of neuroscience High 20631169
2013 CRTC1 functions in the suprachiasmatic nucleus (SCN) to regulate circadian clock entrainment. Light pulses cause CRTC1 to co-activate CREB, inducing Per1 and SIK1 expression. SIK1 then phosphorylates and deactivates CRTC1, providing negative feedback to suppress further light-induced clock shifts. Knockdown of Sik1 in the SCN increased behavioral phase shifts and rapid re-entrainment after experimental jet lag. SCN transcriptome analysis, in vivo Sik1 knockdown (lentiviral shRNA), behavioral phase-shift assays, immunohistochemistry, reporter assays Cell High 23993098
2013 CRTC1 (TORC1) shows rhythmic expression in the SCN and undergoes light-induced nuclear accumulation specifically in early and late subjective night. ChIP analysis confirmed that CRTC1 associates with CREB at the 5′ regulatory region of the Period1 gene; overexpression of CRTC1 markedly upregulates Period1 transcription. CRTC2 does not show photic regulation of subcellular localization in the SCN. Immunohistochemistry, chromatin immunoprecipitation, reporter gene assay, light-pulse paradigm in mice The Journal of neuroscience Medium 23699513
2014 CRTC1 nuclear translocation in hippocampal neurons is regulated by convergence of constitutive kinase pathways and the activity-regulated phosphatase calcineurin. Nuclear CRTC1 binds CREB at IEG promoters in an activity-dependent manner. Forced nuclear expression of CRTC1 in hippocampal neurons activated CREB-dependent transcription and enhanced contextual fear memory. During contextual fear conditioning, endogenous CRTC1 nuclear recruitment occurred in the basolateral amygdala but not hippocampus; CRTC1 knockdown in the amygdala (but not hippocampus) attenuated fear memory. Region-specific viral CRTC1 knockdown, ChIP, immunofluorescence, contextual fear conditioning behavioral assay, reporter assays Neuron High 25277455
2014 CRTC1-MAML2 (C1/M2) oncoprotein gains a novel function by interacting with MYC proteins and activating MYC transcription targets involved in cell growth, metabolism, survival, and tumorigenesis. The C1/M2-MYC interaction is necessary for C1/M2-driven cell transformation. Co-immunoprecipitation, reporter assays, gene expression profiling, transformation assay in human MEC tumor cells Proceedings of the National Academy of Sciences of the United States of America Medium 25071166
2014 In the hippocampus of APPSw,Ind Alzheimer's disease model mice, synaptic activity and spatial memory training induce CRTC1 dephosphorylation at Ser151 and nuclear translocation, and these events are impaired at early pathological and cognitive decline stages. AAV-mediated Crtc1 overexpression in the hippocampus reversed Aβ-induced spatial memory deficits by restoring a specific subset of Crtc1 target genes. AAV-mediated gene delivery, phosphorylation immunoassays, immunohistochemistry, microarray transcriptomics, Morris water maze behavioral testing The Journal of neuroscience High 24760838
2015 CRTC1 is activated by PGE2 signaling in colon cancer cells through EP1 and EP2 receptor-mediated calcineurin and PKA activation, leading to CRTC1 dephosphorylation and nuclear translocation with enhanced CRTC1 transcriptional activity. CRTC1 loss of function reduced viability and cell division; stable CRTC1 overexpression increased xenograft tumor growth. CRTC1-activated genes including NR4A2, COX2, AREG and IL-6 depend on functional AP1 and CREB partners. Pharmacological receptor antagonists, calcineurin inhibitors, PKA modulators, phosphorylation assays, immunofluorescence, siRNA knockdown, stable overexpression, xenograft model, reporter assays Oncogene High 26300003
2016 CRTC1 knockdown in hippocampal neurons impairs associative memory. Context-associative learning (but not single context or unconditioned stimuli alone) induces rapid dephosphorylation of CRTC1 at Ser151 and translocation from cytosol/dendrites to the nucleus, driving expression of c-fos and Nr4a1-3. This CRTC1 activation is disrupted in presenilin conditional double-knockout (neurodegeneration) mice. AAV-mediated CRTC1 gene therapy in the hippocampus ameliorated memory, transcriptional deficits and dendritic degeneration. One-trial contextual fear conditioning, phosphorylation assays, immunohistochemistry, ChIP, gene expression analysis, AAV gene therapy, presenilin cDKO mouse model Biological psychiatry High 27587263
2017 CRTC1 mediates preferential activity-dependent transcription at neuronal CRE/TATA-containing promoters. Neuronal activity and cAMP signals induce CRTC1 dephosphorylation, nuclear translocation, and activity-dependent binding to endogenous CREB; recruitment of CRTC1 to CRE/TATA promoters (c-fos, Dusp1, Nr4a1, Nr4a2, Ptgs2) is activity-dependent, whereas CREB itself is constitutively bound. Genes with CRE/TATA-less promoters are not induced. Chromatin immunoprecipitation, phosphorylation assays, immunofluorescence, luciferase reporter assays, neuronal depolarization/cAMP stimulation Scientific reports Medium 29269871
2018 CRTC1-MAML2 fusion protein induces expression of LINC00473 lncRNA through CREB-mediated transcription, and this depends on the CRTC1-MAML2 ability to activate CREB. LINC00473 is required for MEC cell proliferation and survival in vitro and in vivo. LINC00473 binds the cAMP signaling component NONO, enhancing CRTC1-MAML2-driven CREB-mediated transcription. Lentiviral shRNA knockdown, xenograft tumor model, RNA immunoprecipitation (NONO binding), gene expression profiling, RNA ISH Oncogene Medium 29353885
2019 SIK1 phosphorylates CRTC1, preventing CRTC1 from enhancing CREB transcriptional activity for the expression of osteogenic genes such as Id1. BMP2 suppresses both SIK1 expression and SIK1 activity through PKA-dependent mechanisms to stimulate osteogenesis. SIK1 knockout mice display higher bone mass, osteoblast number, and bone formation rate. SIK1 kinase activity assay, SIK1 knockdown/knockout mice, osteoblast differentiation assays, bone mineralization assays, PKA inhibitor studies, phosphorylation assays Cell death & disease High 31672960
2021 CRTC1-MAML2 is the major oncogenic driver of mucoepidermoid carcinoma (MEC). Doxycycline-induced knockdown of CRTC1-MAML2 blocked growth of established MEC xenografts. Conditional transgenic expression of CRTC1-MAML2 in mice caused 100% penetrant salivary gland tumor formation resembling human MEC histology. CRTC1-MAML2 activates AREG/EGFR signaling; combined CDK4/6 (Palbociclib) and EGFR (Erlotinib) inhibition produced enhanced antitumor responses in vitro and in vivo. Doxycycline-inducible shRNA knockdown, conditional transgenic mouse model, xenograft growth assays, molecular pathway analysis, combination drug treatment in vitro and in vivo JCI insight High 33830080
2021 CRTC1-MAML2 directs transcriptional activation of PGC-1α4 (a non-canonical splice variant), which regulates PPARγ-mediated IGF-1 expression. This autocrine IGF-1 circuit renders MEC cells selectively sensitive to IGF-1R inhibition and PPARγ inverse agonism. Gene expression profiling, small-molecule drug screens, reporter assays, IGF-1R inhibitor treatment, PPARγ inhibitor treatment, primary tumor molecular analysis Cell reports Medium 33626346
2021 NMDAR activation in neurons induces dephosphorylation of CRTC1 at Ser151 and nuclear translocation, where CRTC1 competes with FXR for binding to CREB and drives autophagy gene expression required for late-phase long-term synaptic depression (L-LTD). Disrupting CRTC1-CREB interaction impaired transcription-dependent autophagy and prevented NMDAR-dependent L-LTD. Phosphorylation assays, immunofluorescence, co-immunoprecipitation (CRTC1-CREB, CRTC1-FXR competition), shRNA knockdown, electrophysiology (LTD recordings), autophagy assays Cell reports Medium 34289350
2022 VDAC1 depletion increases free cytosolic Ca2+ in melanocytes, activating calcineurin through the Ca2+-calmodulin-calcineurin pathway, which dephosphorylates CRTC1 to facilitate its nuclear translocation and upregulate MITF transcription, increasing melanogenic gene expression (TYR, TYRP1, TYRP2). VDAC1 siRNA knockdown, Ca2+ imaging, calcineurin activity assay, CRTC1 phosphorylation assays, nuclear fractionation/immunofluorescence, reporter assays, VDAC1 knockout mice Life science alliance Medium 35649693
2022 miR-184-3p directly targets CRTC1 mRNA; downregulation of miR-184-3p in human T2D pancreatic islets leads to upregulation of CRTC1, which protects β-cells from lipotoxicity- and inflammation-induced apoptosis. The protective effect of miR-184-3p inhibition is CRTC1-dependent, as CRTC1 silencing abrogates it. NKX6.1 directly controls miR-184 expression via binding sites in the MIR184 promoter. Chromatin immunoprecipitation (NKX6.1 binding to MIR184 promoter), mRNA and protein expression assays, CRTC1 siRNA silencing, luciferase miRNA target validation, apoptosis assays in human β-cells Cell death discovery Medium 35906204
2006 Sustained expression of Mect1-Maml2 (CRTC1-MAML2) is required for MEC tumor cell growth. RNAi-mediated suppression of the fusion oncogene in parotid and pulmonary MEC cell lines with t(11;19) caused ≥90% colony growth inhibition, which could be partially rescued by co-expressing an RNAi-resistant Mect1-Maml2 mutant. Non-MEC tumor lines lacking the fusion were unaffected. shRNA knockdown, colony formation assay, rescue with RNAi-resistant mutant, in vivo nude mouse xenograft Oncogene High 16652146

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 A reappraisal of the MECT1/MAML2 translocation in salivary mucoepidermoid carcinomas. The American journal of surgical pathology 212 20588178
2013 The CRTC1-SIK1 pathway regulates entrainment of the circadian clock. Cell 177 23993098
2006 MECT1-MAML2 fusion transcript defines a favorable subset of mucoepidermoid carcinoma. Clinical cancer research : an official journal of the American Association for Cancer Research 171 16818685
2016 Splicing factor 1 modulates dietary restriction and TORC1 pathway longevity in C. elegans. Nature 169 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 149 16627617
2017 Regulation of Autophagy through TORC1 and mTORC1. Biomolecules 125 28686223
2005 Transforming activity of MECT1-MAML2 fusion oncoprotein is mediated by constitutive CREB activation. The EMBO journal 123 15961999
2005 Mect1-Maml2 fusion oncogene linked to the aberrant activation of cyclic AMP/CREB regulated genes. Cancer research 114 16103063
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 106 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 102 31411562
2018 Spatially Distinct Pools of TORC1 Balance Protein Homeostasis. Molecular cell 93 30527664
2017 TORC1 organized in inhibited domains (TOROIDs) regulate TORC1 activity. Nature 92 28976958
2017 RNA polymerase III limits longevity downstream of TORC1. Nature 92 29186112
2010 TOR signaling never gets old: aging, longevity and TORC1 activity. Ageing research reviews 92 20385253
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 85 25277455
2014 Crtc1 activates a transcriptional program deregulated at early Alzheimer's disease-related stages. The Journal of neuroscience : the official journal of the Society for Neuroscience 83 24760838
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 81 25767889
2016 Sestrin regulation of TORC1: Is Sestrin a leucine sensor? Science signaling 77 27273098
2008 t(11;19) translocation and CRTC1-MAML2 fusion oncogene in mucoepidermoid carcinoma. Oral oncology 77 18486532
2019 Multilayered Control of Protein Turnover by TORC1 and Atg1. Cell reports 76 31553916
2015 TORC1 and TORC2 work together to regulate ribosomal protein S6 phosphorylation in Saccharomyces cerevisiae. Molecular biology of the cell 74 26582391
2018 Cutaneous Melanocytoma With CRTC1-TRIM11 Fusion: Report of 5 Cases Resembling Clear Cell Sarcoma. The American journal of surgical pathology 68 29240581
2018 The TORC1-Regulated CPA Complex Rewires an RNA Processing Network to Drive Autophagy and Metabolic Reprogramming. Cell metabolism 66 29606597
2014 Molecular architecture and function of the SEA complex, a modulator of the TORC1 pathway. Molecular & cellular proteomics : MCP 66 25073740
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
2020 TORC1 inactivation stimulates autophagy of nucleoporin and nuclear pore complexes. The Journal of cell biology 63 32453403
2021 A TORC1-histone axis regulates chromatin organisation and non-canonical induction of autophagy to ameliorate ageing. eLife 61 33988501
2021 The CRTC1-MAML2 fusion is the major oncogenic driver in mucoepidermoid carcinoma. JCI insight 60 33830080
2015 SEA you later alli-GATOR--a dynamic regulator of the TORC1 stress response pathway. Journal of cell science 58 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
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
2017 CycD/Cdk4 and Discontinuities in Dpp Signaling Activate TORC1 in the Drosophila Wing Disc. Developmental cell 53 28829945
2019 Phosphorus Availability Regulates TORC1 Signaling via LST8 in Chlamydomonas. The Plant cell 51 31712405
2012 TORC1 is required to balance cell proliferation and cell death in planarians. Developmental biology 49 22445864
2017 TORC1-Dependent Phosphorylation Targets in Fission Yeast. Biomolecules 48 28671615
2018 CRTC1-MAML2 fusion-induced lncRNA LINC00473 expression maintains the growth and survival of human mucoepidermoid carcinoma cells. Oncogene 46 29353885
2022 Cutaneous Melanocytic Tumor With CRTC1::TRIM11 Translocation : An Emerging Entity Analyzed in a Series of 41 Cases. The American journal of surgical pathology 44 35993578
2012 TORC1 of fission yeast is rapamycin-sensitive. Genes to cells : devoted to molecular & cellular mechanisms 44 22762302
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
2023 Snf1/AMPK fine-tunes TORC1 signaling in response to glucose starvation. eLife 41 36749016
2009 Enhanced activity of the CREB co-activator Crtc1 in LKB1 null lung cancer. Oncogene 40 20010869
2019 TORC1 specifically inhibits microautophagy through ESCRT-0. Current genetics 39 31041524
2015 Dysregulated CRTC1 activity is a novel component of PGE2 signaling that contributes to colon cancer growth. Oncogene 39 26300003
2021 Neuronal activity recruits the CRTC1/CREB axis to drive transcription-dependent autophagy for maintaining late-phase LTD. Cell reports 38 34289350
2017 CRTC1 mediates preferential transcription at neuronal activity-regulated CRE/TATA promoters. Scientific reports 38 29269871
2021 Conserved and Divergent Mechanisms That Control TORC1 in Yeasts and Mammals. Genes 37 33445779
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
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
2018 The TORC1-Sch9 pathway as a crucial mediator of chronological lifespan in the yeast Saccharomyces cerevisiae. FEMS yeast research 35 29788208
2018 The TORC1-Nem1/Spo7-Pah1/lipin axis regulates microautophagy induction in budding yeast. Biochemical and biophysical research communications 35 30201264
2016 CRTC1 gene is differentially methylated in the human hippocampus in Alzheimer's disease. Alzheimer's research & therapy 35 27094739
2016 CRTC1 Function During Memory Encoding Is Disrupted in Neurodegeneration. Biological psychiatry 35 27587263
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 32 25071166
2021 A glutamine sensor that directly activates TORC1. Communications biology 30 34535752
2022 Manganese is a physiologically relevant TORC1 activator in yeast and mammals. eLife 29 35904415
2021 Salivary mucoepidermoid carcinoma: histological variants, grading systems, CRTC1/3-MAML2 fusions, and clinicopathological features. Histopathology 29 34657306
2021 Fluoride Stimulates Anxiety- and Depression-like Behaviors Associated with SIK2-CRTC1 Signaling Dysfunction. Journal of agricultural and food chemistry 28 34735150
2017 Vacuole-mediated selective regulation of TORC1-Sch9 signaling following oxidative stress. Molecular biology of the cell 28 29237820
2008 Genome-wide expression analysis reveals TORC1-dependent and -independent functions of Sch9. FEMS yeast research 28 18759743
2019 Salt-inducible kinase 1 regulates bone anabolism via the CRTC1-CREB-Id1 axis. Cell death & disease 27 31672960
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
2023 TORC1 Signaling in Fungi: From Yeasts to Filamentous Fungi. Microorganisms 23 36677510
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 A spatially and functionally distinct pool of TORC1 defines signaling endosomes in yeast. Autophagy 22 30732525
2022 Localization of a TORC1-eIF4F translation complex during CD8+ T cell activation drives divergent cell fate. Molecular cell 21 35597236
2017 TORC1-mediated sensing of chaperone activity alters glucose metabolism and extends lifespan. Aging cell 21 28613034
2025 SIK2 mediated mitochondrial homeostasis in spinal cord injury: modulating oxidative stress and the AIM2 inflammasome via CRTC1/CREB signaling. Journal of neuroinflammation 20 41339921
2023 The TORC1 activates Rpd3L complex to deacetylate Ino80 and H2A.Z and repress autophagy. Science advances 20 36888706
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
2022 V-ATPase/TORC1-mediated ATFS-1 translation directs mitochondrial UPR activation in C. elegans. The Journal of cell biology 20 36314986
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 Import of extracellular ATP in yeast and man modulates AMPK and TORC1 signalling. Journal of cell science 18 30814334
2018 Multilayered regulation of TORC1-body formation in budding yeast. Molecular biology of the cell 18 30485160
2010 CRTC1 expression during normal and abnormal salivary gland development supports a precursor cell origin for mucoepidermoid cancer. Gene expression patterns : GEP 18 20837164
2021 CRTC1/MAML2 directs a PGC-1α-IGF-1 circuit that confers vulnerability to PPARγ inhibition. Cell reports 17 33626346
2020 Clinicopathological significance of EGFR pathway gene mutations and CRTC1/3-MAML2 fusions in salivary gland mucoepidermoid carcinoma. Histopathology 17 32129900
2020 TORC1 signaling regulates cytoplasmic pH through Sir2 in yeast. Aging cell 17 32449834
2019 (Epi)genetic regulation of CRTC1 in human eating behaviour and fat distribution. EBioMedicine 17 31153815
2019 TORC1, Tel1/Mec1, and Mpk1 regulate autophagy induction after DNA damage in budding yeast. Cellular signalling 16 31201849
2018 Cdc14 Phosphatase Promotes TORC1-Regulated Autophagy in Yeast. Journal of molecular biology 15 29694832
2022 VDAC1 negatively regulates melanogenesis through the Ca2+-calcineurin-CRTC1-MITF pathway. Life science alliance 14 35649693
2018 The TORC1 signaling pathway regulates respiration-induced mitophagy in yeast. Biochemical and biophysical research communications 14 29787763
2018 Yeast thioredoxin reductase Trr1p controls TORC1-regulated processes. Scientific reports 14 30405153
2023 Pib2 is a cysteine sensor involved in TORC1 activation in Saccharomyces cerevisiae. Cell reports 13 38127619
2020 CRTC1 signaling involvement in depression-like behavior of prenatally stressed offspring rat. Behavioural brain research 13 33161032
2018 Epigenetic regulation of Fgf1 transcription by CRTC1 and memory enhancement. Brain research bulletin 13 29477835
2022 Slt2 Is Required to Activate ER-Stress-Protective Mechanisms through TORC1 Inhibition and Hexosamine Pathway Activation. Journal of fungi (Basel, Switzerland) 12 35205847
2019 The TORC1 inhibitor Nprl2 protects age-related digestive function in Drosophila. Aging 12 31712450

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