PI3K/AKT/mTOR signaling in cancer

DYRK1A Interacts with the Tuberous Sclerosis Complex and Promotes mTORC1 Activity

This study identifies DYRK1A's role in promoting mTORC1 activity by inhibiting TSC complex activity through phosphorylation of TSC2, and shows conservation in Drosophila.

AKT-mediated phosphorylation of TSC2 controls stimulus and tissue-specific mTORC1 signaling and organ growth

This study shows that AKT-mediated phosphorylation of TSC2 regulates tissue-specific mTORC1 signaling and organ growth in mice.

Stress granule formation enables anchorage-independence survival in cancer cells

This study shows stress granules enhance survival of breast cancer cells under anoikis stress and identifies a signaling pathway that promotes their formation, suggesting therapeutic targeting of stress granules could improve cancer treatment.

The RNA binding protein Pub1 inhibits TORC1 activity in Saccharomyces cerevisiae

This study shows that Pub1, an RNA binding protein, inhibits TORC1 activity by promoting its aggregation into ribonucleoprotein complexes in yeast.

PDK-1/S6K and mTORC1 bypass systemic growth restrictions to promote regeneration

The paper identifies a metabolic pathway involving Pdk1/S6K and mTORC1 that allows regenerating tissues to bypass systemic growth restrictions induced by inflammation.

mTORC1 ACTIVATION IN PRESUMED CLASSICAL MONOCYTES:OBSERVED CORRELATES WITH HUMAN SIZE VARIATION AND NEUROPSYCHIATRIC DISEASE

The paper measures mTORC1 activity via phosphorylated p70S6K in psychiatric patients and finds it correlates with body structure and medication response to ketamine and rapamycin.

mTORC1 activity oscillates throughout the cell cycle promoting mitotic entry and differentially influencing autophagy induction

This study shows mTORC1 activity oscillates during the cell cycle, peaks in S and G2, and is lowest in mitosis and G1, with distinct regulatory mechanisms and functional consequences.

Down-regulation of AKT proteins slows the growth of mutant-KRAS pancreatic tumors

This study shows that down-regulating AKT proteins slows mutant-KRAS pancreatic tumor growth more effectively than inhibiting AKT kinase activity.

PI3 kinase-unrelated effects of LY294002 and LY303511 on serotonin-induced Ca2+ and cAMP signaling

This study investigates the effects of PI3K inhibitors LY294002 and LY303511 on serotonin-induced Ca2+ and cAMP signaling, revealing PI3K-unrelated receptor-specific effects.

Loop modelling provides insights into regulation of mTORC1 activity via DEPTOR dimerisation

The paper models DEPTOR dimerisation and its interaction with mTORC1 to elucidate how linker phosphorylation affects mTORC1 inhibition.

mTORC1 is required for differentiation of germline stem cells in the Drosophila melanogaster testis

This study shows that mTORC1 is essential for differentiation of germline stem cells in Drosophila melanogaster testis, with Tor downregulation causing differentiation block and somatic cell activation.

Distinct roles of LARP1 and 4EBP1/2 in regulating translation and stability of 5'TOP mRNAs

This study investigates the roles of LARP1 and 4EBP1/2 in regulating translation and stability of 5'TOP mRNAs using single-molecule imaging, showing 4EBP1/2's dominant repression and LARP1's selective protection.

Structure-based engineering of Tor complexes uncovers different roles of two types of yeast TORC1s

The paper engineers yeast TORC1 complexes to reveal distinct functional roles of Tor1- and Tor2-containing TORC1s in growth and lifespan.

MTOR modulation induces selective perturbations in histone methylation which influence the anti-proliferative effects of mTOR inhibitors

This study shows that both mTOR activation and inhibition increase H3K27me3 through distinct mechanisms, and this epigenetic change correlates with the anti-proliferative effects of mTOR inhibitors.

Genomic dissection and mutation-specific target discovery for breast cancer PIK3CA hotspot mutations

The paper identifies mutation-specific targets for PIK3CA hotspot mutations using a multi-modal genomics approach and isogenic cell lines.

Oncogenic PIK3CA corrupts growth factor signaling specificity

The paper uses single-cell analyses to show that oncogenic PIK3CAH1047R reduces IGF1 signaling specificity and enhances EGF responses, leading to increased phenotypic heterogeneity.

Hyperactivity of mTORC1 and mTORC2-dependent signaling mediate epilepsy downstream of somatic PTEN loss.

This study shows that both mTORC1 and mTORC2 hyperactivity contribute to epilepsy caused by somatic PTEN loss, and that inhibiting both complexes can normalize brain activity.

Metabolism of glucose activates TORC1 through multiple mechanisms in Saccharomyces cerevisiae

This study identifies three distinct pathways by which glucose metabolism activates TORC1 in yeast, including both Rag GTPase-dependent and independent mechanisms.

Protein interaction network analysis of mTOR signaling reveals modular organization

The paper analyzes the mTOR protein interaction network to reveal its modular organization and how it responds to kinase inhibitors.

MTORC2 is a physiological hydrophobic motif kinase of S6 Kinase 1.

This paper identifies mTORC2 as the physiological kinase responsible for hydrophobic motif phosphorylation of S6K1, demonstrating its activation after auto-inhibition by mTORC1.

TORC1 phosphorylates and inhibits the ribosome preservation factor Stm1 to activate dormant ribosomes

The paper shows that TORC1 inhibits Stm1 to reactivate dormant ribosomes, revealing an evolutionarily conserved mechanism for ribosome preservation.

TOR signalling regulates epithelial cell shape transition in Drosophila oogenesis

This study shows TOR signaling regulates epithelial cell shape transition in Drosophila oogenesis by modulating endocytosis and PAR-1-mediated removal of Fasciclin 2.

Mathematical modelling of brain mTOR activity identifies selective vulnerability of cell types and signalling pathways

The paper uses mathematical modeling to analyze mTOR pathway activity in human brain cells, identifying cell-type-specific responses to ligands and changes in Alzheimer's Disease.

Phosphorylation of the novel mTOR substrate Unkempt regulates cellular morphogenesis

This study identifies Unkempt as a novel mTORC1 substrate whose phosphorylation regulates cellular morphology by inhibiting its ability to induce bipolar morphology.

Sfp1 integrates TORC1 and PKA activity towards yeast ribosome biogenesis

This study identifies PKA and TORC1 phosphorylation sites on Sfp1 and shows how these pathways regulate its localization and function in yeast ribosome biogenesis.

Synergistic Combined-proteomics Guided Mapping strategy identifies mTOR mediated phosphorylation of LARP1 in nutrient responsiveness and dilated cardiomyopathy

The paper identifies mTOR-mediated phosphorylation of LARP1 using a combined proteomics strategy and links it to nutrient responsiveness and dilated cardiomyopathy.

TORC1 and PKA activity towards ribosome biogenesis oscillates in synchrony with the budding yeast cell cycle

The paper shows that TORC1 and PKA activity related to ribosome biogenesis oscillates with the budding yeast cell cycle under constant conditions.

Dopamine neuron morphology and output are differentially controlled by mTORC1 and mTORC2

This study investigates how mTORC1 and mTORC2 differentially regulate dopamine neuron morphology and function in mice, revealing distinct effects on structure, excitability, and dopamine output.

FER-mediated tyrosine phosphorylation and PIK3R2/p85β recruitment on IRS4 promotes the PI3K-AKT signaling pathway and tumorigenesis in ovarian cancer

The paper identifies FER-mediated tyrosine phosphorylation of IRS4 and its role in activating the PI3K-AKT pathway, contributing to ovarian cancer tumorigenesis.

Detailed Clinical and Functional Studies of New MTOR Variants in Smith-Kingsmore Syndrome Reveal Deficits of Circadian and Sleep Homeostasis

This study identifies new MTOR variants in Smith-Kingsmore Syndrome, reveals circadian and sleep deficits, and shows rapamycin treatment can improve symptoms.