ArticleMolecular and cellular biology2004
Cooperative regulation of the cell division cycle by the protein kinases RAF and AKT.
Article in Molecular and cellular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.
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- Special Issue "Cancer Biomarker: Current Status and Future Perspectives".International journal of molecular sciences · 2025Article
- Synergistic effect of bazedoxifene and abemaciclib co‑treatment in triple‑negative breast cancer cells in vitro.Oncology letters · 2024Article
- Bta-miR-665 improves bovine blastocyst development through its influence on microtubule dynamics and apoptosis.Frontiers in genetics · 2024Article
- VGLUT3 Deletion Rescues Motor Deficits and Neuronal Loss in the zQ175 Mouse Model of Huntington's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Review
- Nitrate increases cisplatin chemosensitivity of oral squamous cell carcinoma via REDD1/AKT signaling pathway.Science China. Life sciences · 2021Article
- Review
- The Biology of Classic Hairy Cell Leukemia.International journal of molecular sciences · 2021Review
- Inhibition of RAF dimers: it takes two to tango.Biochemical Society transactions · 2021Review
- Review
- Mutant Kras-induced upregulation of CD24 enhances prostate cancer stemness and bone metastasis.Oncogene · 2019Article
- Cholesterol-enriched membrane microdomains are needed for insulin signaling and proliferation in hepatic cells.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Osteogenic Effect and Cell Signaling Activation of Extremely Low-Frequency Pulsed Electromagnetic Fields in Adipose-Derived Mesenchymal Stromal Cells.Stem cells international · 2018Article
- Review
- The miR-106a~363Oncotarget · 2017Article
- Caudal migration and proliferation of renal progenitors regulates early nephron segment size in zebrafish.Scientific reports · 2016Article
- Pluripotency transcription factors in lung cancer-a review.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
The RAS-activated RAF-->MEK-->extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3'-kinase (PI3'-kinase)-->PDK1-->AKT signaling pathways are believed to cooperate to promote the proliferation of normal cells and the aberrant proliferation of cancer cells. To explore the mechanisms that underlie such cooperation, we have derived cells harboring conditionally active, steroid hormone-regulated forms of RAF and AKT. These cells permit the assessment of the biological and biochemical effects of activation of these protein kinases either alone or in combination with one another. Under conditions where activation of neither RAF nor AKT alone promoted S-phase progression, coactivation of both kinases elicited a robust proliferative response. Moreover, under conditions where high-level activation of RAF induced G(1) cell cycle arrest, activation of AKT bypassed the arrest and promoted S-phase progression. At the level of the cell cycle machinery, RAF and AKT cooperated to induce cyclin D1 and repress p27(Kip1) expression. Repression of p27(Kip1) was accompanied by a dramatic reduction in KIP1 mRNA and was observed in primary mouse embryo fibroblasts derived from mice either lacking SKP2 or expressing a T187A mutated form of p27(Kip1). Consistent with these observations, pharmacological inhibition of MEK or PI3'-kinase inhibited the effects of activated RAS on the expression of p27(Kip1) in NIH 3T3 fibroblasts and in a panel of bona fide human pancreatic cancer cell lines. Furthermore, we demonstrated that AKT activation led to sustained activation of cyclin/cdk2 complexes that occurred concomitantly with the removal of RAF-induced p21(Cip1) from cyclin E/cdk2 complexes. Cumulatively, these data strongly suggest that the RAF-->MEK-->ERK and PI3'K-->PDK-->AKT signaling pathways can cooperate to promote G(0)-->G(1)-->S-phase cell cycle progression in both normal and cancer cells.
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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.