ArticleMolecular and cellular biology2007
Tuberous sclerosis complex proteins 1 and 2 control serum-dependent translation in a TOP-dependent and -independent manner.
Article in Molecular and cellular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 70 citations in OpenAlex.
- Convergent and Divergent Molecular Pathways in FMR1-, TSC2- and FMR1/TSC2 Knockout Neurons.Molecular neurobiology · 2026Article
- Larp1 supports brain growth and spatial memory via post-transcriptional control of the translation machinery.bioRxiv : the preprint server for biology · 2025Article
- Dysregulated acetylcholine-mediated dopamine neurotransmission in the eIF4E Tg mouse model of autism spectrum disorders.Cell reports · 2024Article
- Translatome analysis of tuberous sclerosis complex 1 patient-derived neural progenitor cells reveals rapamycin-dependent and independent alterations.Molecular autism · 2023Article
- Iron drives anabolic metabolism through active histone demethylation and mTORC1.Nature cell biology · 2023Article
- B cell receptor signaling in germinal centers prolongs survival and primes B cells for selection.Immunity · 2023Article
- Patient-derived xenografts and in vitro model show rationale for imatinib mesylate repurposing in HEY1-NCoA2-driven mesenchymal chondrosarcoma.Laboratory investigation; a journal of technical methods and pathology · 2022Article
- Heterogeneity and Cancer-Related Features in Lymphangioleiomyomatosis Cells and Tissue.Molecular cancer research : MCR · 2021Article
- Translational control in neurovascular brain development.Royal Society open science · 2021Review
- Exon junction complex dependent mRNA localization is linked to centrosome organization during ciliogenesis.Nature communications · 2021Article
- Ribosome profiling in mouse hippocampus: plasticity-induced regulation and bidirectional control by TSC2 and FMRP.Molecular autism · 2020Article
- Hematopoietic Stem and Progenitor Cells Exhibit Stage-Specific Translational Programs via mTOR- and CDK1-Dependent Mechanisms.Cell stem cell · 2020Article
- Enhanced translation expands the endo-lysosome size and promotes antigen presentation during phagocyte activation.PLoS biology · 2019Article
- Antigen Complexed with a TLR9 Agonist Bolsters c-Myc and mTORC1 Activity in Germinal Center B Lymphocytes.ImmunoHorizons · 2019Article
- CBAP modulates Akt-dependent TSC2 phosphorylation to promote Rheb-mTORC1 signaling and growth of T-cell acute lymphoblastic leukemia.Oncogene · 2019Article
- Article
- Oligodendrocyte precursor cell-intrinsic effect of Rheb1 controls differentiation and mediates mTORC1-dependent myelination in brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Oxygen sufficiency controls TOP mRNA translation via the TSC-Rheb-mTOR pathway in a 4E-BP-independent manner.Journal of molecular cell biology · 2014Article
- Translational control of immune responses: from transcripts to translatomes.Nature immunology · 2014Review
- Regulation of protein translation and c-Jun expression by prostate tumor overexpressed 1.Oncogene · 2014Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tuberous sclerosis complex (TSC) proteins TSC1 and TSC2 regulate protein translation by inhibiting the serine/threonine kinase mTORC1 (for mammalian target of rapamycin complex 1). However, how TSC1 and TSC2 control overall protein synthesis and the translation of specific mRNAs in response to different mitogenic and nutritional stimuli is largely unknown. We show here that serum withdrawal inhibits mTORC1 signaling, causes disassembly of translation initiation complexes, and causes mRNA redistribution from polysomes to subpolysomes in wild-type mouse embryo fibroblasts (MEFs). In contrast, these responses are defective in Tsc1(-/-) or Tsc2(-/-) MEFs. Microarray analysis of polysome- and subpolysome-associated mRNAs uncovered specific mRNAs that are translationally regulated by serum, 90% of which are TSC1 and TSC2 dependent. Surprisingly, the mTORC1 inhibitor, rapamycin, abolished mTORC1 activity but only affected approximately 40% of the serum-regulated mRNAs. Serum-dependent signaling through mTORC1 and polysome redistribution of global and individual mRNAs were restored upon re-expression of TSC1 and TSC2. Serum-responsive mRNAs that are sensitive to inhibition by rapamycin are highly enriched for terminal oligopyrimidine and for very short 5' and 3' untranslated regions. These data demonstrate that the TSC1/TSC2 complex regulates protein translation through mainly mTORC1-dependent mechanisms and implicates a discrete profile of deregulated mRNA translation in tuberous sclerosis pathology.
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