ArticleThe Journal of biological chemistry2015
Rictor Undergoes Glycogen Synthase Kinase 3 (GSK3)-dependent, FBXW7-mediated Ubiquitination and Proteasomal Degradation.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 96 citations in OpenAlex.
- The role of mTORC2/RICTOR in immune cells and inflammatory diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Targeting the GSK-3β/mTOR axis: a novel pharmacological strategy for preeclampsia prevention and treatment.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Article
- FBXO22 inhibits colitis and colorectal carcinogenesis by regulating the degradation of the S2448-phosphorylated form of mTOR.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Stress resilience is an active and multifactorial process manifested by structural, functional, and molecular changes in synapses.Neurobiology of stress · 2024Article
- Molecular insights and clinical implications for the tumor suppressor role of SCFBiochimica et biophysica acta. Reviews on cancer · 2024Review
- The HTLV-I oncoprotein Tax inactivates the tumor suppressor FBXW7.Journal of virology · 2024Article
- RICTOR/mTORC2 downregulation in BRAFMolecular cancer · 2024Article
- The mTORC2 signaling network: targets and cross-talks.The Biochemical journal · 2024Review
- Functional analysis reveals driver cooperativity and novel mechanisms in endometrial carcinogenesis.EMBO molecular medicine · 2023Article
- Regulation of mTOR Signaling: Emerging Role of Cyclic Nucleotide-Dependent Protein Kinases and Implications for Cardiometabolic Disease.International journal of molecular sciences · 2023Review
- An innate pathogen sensing strategy involving ubiquitination of bacterial surface proteins.Science advances · 2023Article
- Pharmacological vitamin C inhibits mTOR signaling and tumor growth by degrading Rictor and inducing HMOX1 expression.PLoS genetics · 2023Article
- A novel polypeptide encoded by the circular RNA ZKSCAN1 suppresses HCC via degradation of mTOR.Molecular cancer · 2023Article
- Decrypting a path based approach for identifying the interplay between PI3K and GSK3 signaling cascade from the perspective of cancer.Genes & diseases · 2022Review
- High glutamine suppresses osteogenesis through mTORC1-mediated inhibition of the mTORC2/AKT-473/RUNX2 axis.Cell death discovery · 2022Article
- Reprogramming dysfunctional CD8+ T cells to promote properties associated with natural HIV control.The Journal of clinical investigation · 2022Article
- Review
- Leukemia inhibitory factor receptor homodimerization mediated by acetylation of extracellular lysine promotes prostate cancer progression through the PDPK1/AKT/GCN5 axis.Clinical and translational medicine · 2022Article
- CDK1/FBXW7 facilitates degradation and ubiquitination of MLST8 to inhibit progression of renal cell carcinoma.Cancer science · 2022Article
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Authors and funding
5 authors at 1 institution in 1 country.
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Abstract
Rictor, an essential component of mTOR complex 2 (mTORC2), plays a pivotal role in regulating mTOR signaling and other biological functions. Posttranslational regulation of rictor (e.g. via degradation) and its underlying mechanism are largely undefined and thus are the focus of this study. Chemical inhibition of the proteasome increased rictor ubiquitination and levels. Consistently, inhibition of FBXW7 with various genetic means including knockdown, knock-out, and enforced expression of a dominant-negative mutant inhibited rictor ubiquitination and increased rictor levels, whereas enforced expression of FBXW7 decreased rictor stability and levels. Moreover, we detected an interaction between FBXW7 and rictor. Hence, rictor is degraded through an FBXW7-mediated ubiquitination/proteasome mechanism. We show that this process is dependent on glycogen synthase kinase 3 (GSK3): GSK3 was associated with rictor and directly phosphorylated the Thr-1695 site in a putative CDC4 phospho-degron motif of rictor; mutation of this site impaired the interaction between rictor and FBXW7, decreased rictor ubiquitination, and increased rictor stability. Finally, enforced activation of Akt enhanced rictor levels and increased mTORC2 activity as evidenced by increased formation of mTORC2 and elevated phosphorylation of Akt, SGK1, and PKCα. Hence we suggest that PI3K/Akt signaling may positively regulate mTORC2 signaling, likely through suppressing GSK3-dependent rictor degradation.
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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.