ArticleOncotarget2015
Rapamycin inhibits mSin1 phosphorylation independently of mTORC1 and mTORC2.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Review
- Unbiased evaluation of rapamycin's specificity as an mTOR inhibitor.Aging cell · 2023Article
- Recent advances of the mammalian target of rapamycin signaling in mesenchymal stem cells.Frontiers in genetics · 2022Review
- Therapeutic mTOR blockade in systemic autoimmunity: Implications for antiviral immunity and extension of lifespan.Autoimmunity reviews · 2021Review
- Down-regulated LncR-MALAT1 suppressed cell proliferation and migration by inactivating autophagy in bladder cancer.RSC advances · 2018Article
- Rapamycin attenuates BAFF-extended proliferation and survival via disruption of mTORC1/2 signaling in normal and neoplastic B-lymphoid cells.Journal of cellular physiology · 2018Article
- Ciclopirox activates ATR-Chk1 signaling pathway leading to Cdc25A protein degradation.Genes & cancer · 2018Article
- SKLB188 inhibits the growth of head and neck squamous cell carcinoma by suppressing EGFR signalling.British journal of cancer · 2017Article
- Peptidylprolyl Isomerases as In Vivo Carriers for Drugs That Target Various Intracellular Entities.Biomolecules · 2017Review
- Ciclopirox inhibits cancer cell proliferation by suppression of Cdc25A.Genes & cancer · 2017Article
- mTOR function and therapeutic targeting in breast cancer.American journal of cancer research · 2017Review
- Proteomic analysis reveals GIT1 as a novel mTOR complex component critical for mediating astrocyte survival.Genes & development · 2016Article
- Molecular Pathways: Increased Susceptibility to Infection Is a Complication of mTOR Inhibitor Use in Cancer Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Review
- A high-throughput kinome screen reveals serum/glucocorticoid-regulated kinase 1 as a therapeutic target for NF2-deficient meningiomas.Oncotarget · 2015Article
- Effect of rapamycin (RAPA) on the growth of lung cancer and its mechanism in mice with A549.International journal of clinical and experimental pathology · 2015Article
- mTOR kinase inhibition disrupts neuregulin 1-ERBB3 autocrine signaling and sensitizes NF2-deficient meningioma cellular models to IGF1R inhibition.The Journal of biological chemistryArticle
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Current knowledge indicates that the mammalian target of rapamycin (mTOR) functions as two complexes, mTORC1 and mTORC2, regulating cell growth, proliferation, survival, differentiation, and motility. Recently mSin1 has been identified as a critical component of mTORC2, which is essential for phosphorylation of Akt and other signaling molecules. Studies have shown that rapamycin inhibits phosphorylation of mSin1. However, the underlying mechanism is unknown. Here we found that rapamycin inhibited phosphorylation of mSin1 potently and rapidly. Expression of rapamycin-resistant mutant of mTOR (mTOR-T), but not rapamycin-resistant and kinase dead mutant of mTOR (mTOR-TE), prevented rapamycin from inhibiting mSin1 phosphorylation, suggesting that rapamycin-induced dephosphorylation of mSin1 is mTOR-dependent. Surprisingly, ectopic expression of rapamycin-resistant and constitutively active p70 S6 kinase 1 (S6K1) did not confer resistance to rapamycin-induced dephosphorylation of mSin1. Furthermore, disruption of mTORC1 and mTORC2 by silencing raptor and rictor, respectively, or downregulation of S6K1 or Akt did not induce the dephosphorylation of mSin1 as rapamycin did. However, silencing mTOR or mLST8 mimicked the effect of rapamycin, inhibiting mSin1 phosphorylation. Our findings suggest that rapamycin inhibits mSin1 phosphorylation, which is independent of mTORC1 and mTORC2, but is possibly dependent on a new mTOR complex, which at least contains mTOR and mLST8.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.