ArticleMolecular and cellular biology2010
Mitotic raptor promotes mTORC1 activity, G(2)/M cell cycle progression, and internal ribosome entry site-mediated mRNA translation.
Article in Molecular and cellular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 97 citations in OpenAlex.
- Spatiotemporal Expression Inversion ofAnimals : an open access journal from MDPI · 2026Article
- Cell Type-Specific mTORC1 Signaling and Translational Control in Synaptic Plasticity and Memory.Journal of neurochemistry · 2025Review
- The kinase PLK1 promotes Hedgehog signaling-dependent resistance to the antiandrogen enzalutamide in metastatic prostate cancer.Science signaling · 2025Article
- mTORC1 activity oscillates throughout the cell cycle, promoting mitotic entry and differentially influencing autophagy induction.Cell reports · 2024Article
- Polyploidy and mTOR signaling: a possible molecular link.Cell communication and signaling : CCS · 2024Review
- Expression of mTOR in normal and pathological conditions.Molecular cancer · 2023Review
- DNA-dependent protein kinase catalytic subunit (DNA-PKcs) drives chronic kidney disease progression in male mice.Nature communications · 2023Article
- Bi-allelic TTI1 variants cause an autosomal-recessive neurodevelopmental disorder with microcephaly.American journal of human genetics · 2023Article
- Melatonin as a regulator of apoptosis in leukaemia: molecular mechanism and therapeutic perspectives.Frontiers in pharmacology · 2023Review
- Apoptosis as a Barrier against CIN and Aneuploidy.Cancers · 2022Review
- Systems Biology Analysis of Temporal Dynamics That Govern Endothelial Response to Cyclic Stretch.Biomolecules · 2022Review
- eIF3a regulation of mTOR signaling and translational control via HuR in cellular response to DNA damage.Oncogene · 2022Article
- Lysosomal Changes in Mitosis.Cells · 2022Article
- Glycogen synthesis and beyond, a comprehensive review of GSK3 as a key regulator of metabolic pathways and a therapeutic target for treating metabolic diseases.Medicinal research reviews · 2022Review
- CHERP Regulates the Alternative Splicing of pre-mRNAs in the Nucleus.International journal of molecular sciences · 2022Article
- TORC1 inactivation promotes APC/C-dependent mitotic slippage in yeast and human cells.iScience · 2022Article
- Review
- The Roles of Post-Translational Modifications on mTOR Signaling.International journal of molecular sciences · 2021Review
- A cyclin-dependent kinase, CDK11/p58, represses cap-dependent translation during mitosis.Cellular and molecular life sciences : CMLS · 2020Article
- Regulation of mTORC1 by Upstream Stimuli.Genes · 2020Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mTOR signaling complex integrates signals from growth factors and nutrient availability to control cell growth and proliferation, in part through effects on the protein-synthetic machinery. Protein synthesis rates fluctuate throughout the cell cycle but diminish significantly during the G(2)/M transition. The fate of the mTOR complex and its role in coordinating cell growth and proliferation signals with protein synthesis during mitosis remain unknown. Here we demonstrate that the mTOR complex 1 (mTORC1) pathway, which stimulates protein synthesis, is actually hyperactive during mitosis despite decreased protein synthesis and reduced activity of mTORC1 upstream activators. We describe previously unknown G(2)/M-specific phosphorylation of a component of mTORC1, the protein raptor, and demonstrate that mitotic raptor phosphorylation alters mTORC1 function during mitosis. Phosphopeptide mapping and mutational analysis demonstrate that mitotic phosphorylation of raptor facilitates cell cycle transit through G(2)/M. Phosphorylation-deficient mutants of raptor cause cells to delay in G(2)/M, whereas depletion of raptor causes cells to accumulate in G(1). We identify cyclin-dependent kinase 1 (cdk1 [cdc2]) and glycogen synthase kinase 3 (GSK3) pathways as two probable mitosis-regulated protein kinase pathways involved in mitosis-specific raptor phosphorylation and altered mTORC1 activity. In addition, mitotic raptor promotes translation by internal ribosome entry sites (IRES) on mRNA during mitosis and is demonstrated to be associated with rapamycin resistance. These data suggest that this pathway may play a role in increased IRES-dependent mRNA translation during mitosis and in rapamycin insensitivity.
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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.