ArticleOncogene2016
SUMO modification of Akt regulates global SUMOylation and substrate SUMOylation specificity through Akt phosphorylation of Ubc9 and SUMO1.
Article in Oncogene, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 77 citations in OpenAlex.
- The regulatory role of post-translational modifications in the pathogenesis of ulcerative colitis.Molecular biology reports · 2026Review
- Targeting SUMOylation in glioblastoma: A novel avenue for therapy and biomarker discovery.Genes & diseases · 2026Review
- Review
- DNA double strand break repair: a model of specificity and complexity in SUMO signalling.Essays in biochemistry · 2025Review
- Non-covalent SUMO interactions with ligases and effectors: SUMO-interacting motifs and beyond.Essays in biochemistry · 2025Review
- Simulated Microgravity-Induced Changes in SUMOylation and Protein Expression inInternational journal of molecular sciences · 2025Article
- Synthetic inhibition of the SUMO pathway by targeting the SAE1 component via TAK-981 compound impairs growth and chemosensitizes embryonal and alveolar rhabdomyosarcoma cell lines.Molecular and cellular biochemistry · 2025Article
- APP SUMOylation prevents BACE1 cleavage of APP and increases BACE1 degradation to promote the nonamyloidogenic pathway.Molecular medicine (Cambridge, Mass.) · 2025Article
- The role of SUMOylation in epithelial-mesenchymal transition.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Reactive Oxygen Species: A Double-Edged Sword in the Modulation of Cancer Signaling Pathway Dynamics.Cells · 2025Review
- AKT kinases as therapeutic targets.Journal of experimental & clinical cancer research : CR · 2024Review
- Genetic Code Expansion Approaches to Decipher the Ubiquitin Code.Chemical reviews · 2024Review
- SUMOylation of Warts kinase promotes neural stem cell reactivation.Nature communications · 2024Article
- Crosstalk between SUMOylation and other post-translational modifications in breast cancer.Cellular & molecular biology letters · 2024Review
- Mechanisms and functions of SUMOylation in health and disease: a review focusing on immune cells.Journal of biomedical science · 2024Review
- Stabilization of Pin1 by USP34 promotes Ubc9 isomerization and protein sumoylation in glioma stem cells.Nature communications · 2024Article
- Multi-faceted regulation of CREB family transcription factors.Frontiers in molecular neuroscience · 2024Review
- Distinctive tumorigenic significance and innovative oncology targets of SUMOylation.Theranostics · 2024Review
- AKT1 induces Nanog promoter in a SUMOylation-dependent manner in different pluripotent contexts.BMC research notes · 2023Article
- Signalling mechanisms and cellular functions of SUMO.Nature reviews. Molecular cell biology · 2022Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SUMOylation is an important post-translational modification, and Akt SUMOylation was found to regulate cell proliferation, tumorigenesis and cell cycle, but the molecular mechanism of Akt SUMOylation is less well known. Here, we show both endogenous and ectopic Akt SUMOylation and Lys276 is the major SUMO acceptor on Akt. Further, Akt SUMOylation is Akt phosphorylation dependent and Akt SUMOylation increases Akt kinase activity without affecting the phosphorylation level of Akt. Moreover, endogenous Akt SUMOylation is enhanced by insulin treatment and this is Akt activity dependent. Heat-shock stimulus also increases Akt SUMOylation and it is also Akt activity dependent. Endogenous Akt SUMOylation is also found in the rat brain and it is enhanced by insulin-like growth factor-1 stimulation. In addition, Akt directly phosphorylates Ubc9 at Thr35 and phosphorylates SUMO1 at Thr76. Ubc9 phosphorylation at Thr35 promotes Ubc9 thioester bond formation and SUMO1 phosphorylation at Thr76 stabilizes the SUMO1 protein. Through these distinct mechanisms, Akt SUMOylation regulates global SUMOylation, including Akt and Ubc9 SUMOylation, and substrate SUMOylation specificity, including STAT1 and CREB SUMOylation, in different manners. Akt SUMOylation also enhances phosphatase and tensin homolog (PTEN) SUMOylation through Akt phosphorylation of Ubc9 and SUMO1, which serves as an endogenous mechanism to stop the positive feedback loop resulted from Akt activation. Further, Akt SUMOylation increases cyclin D1 expression and cell proliferation, and these effects are also mediated through Ubc9 phosphorylation at Thr35 and SUMO1 phosphorylation at Thr76. Here, we have identified a novel mechanism for SUMOylation regulation. Because of the important role Akt plays in tumorigenesis, this mechanism may also be involved in Akt-regulated tumorigenesis.
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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.