ArticleThe Journal of clinical investigation2016
CDK4 is an essential insulin effector in adipocytes.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 46 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
46 citing papers in PubMed, 82 citations in OpenAlex.
- Clinical Implications of Body Mass Index in Metastatic Breast Cancer Patients Treated With Abemaciclib and Endocrine Therapy.Journal of the National Cancer Institute · 2021Trial
- Alternate actions of CDK4/6 inhibitors beyond cell cycle blockade: unexplored roles in therapy resistance.Cancer metastasis reviews · 2025Review
- The impact of body mass index on the progression-free survival of CDK 4/6 inhibitors in metastatic breast cancer patients.Future oncology (London, England) · 2024Article
- Review
- Article
- Oxidative stress-induced FAK activation contributes to uterine serous carcinoma aggressiveness.Molecular oncology · 2023Article
- Evaluation of the relationship between toxicity of cyclin-dependent kinase 4/6 inhibitors and body surface area.Revista da Associacao Medica Brasileira (1992) · 2023Article
- The role of miR-369-3p in proliferation and differentiation of preadipocytes in Aohan fine-wool sheep.Archives animal breeding · 2023Article
- Cellular and Molecular Mechanisms and Effects of Berberine on Obesity-Induced Inflammation.Biomedicines · 2022Article
- The Senescence Markers p16INK4A, p14ARF/p19ARF, and p21 in Organ Development and Homeostasis.Cells · 2022Review
- Article
- Co-occurrence CDK4/6 amplification serves as biomarkers of de novo EGFR TKI resistance in sensitizing EGFR mutation non-small cell lung cancer.Scientific reports · 2022Article
- TTC39B destabilizes retinoblastoma protein promoting hepatic lipogenesis in a sex-specific fashion.Journal of hepatology · 2022Article
- Obesity and endocrine therapy resistance in breast cancer: Mechanistic insights and perspectives.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2022Review
- The SREBP-dependent regulation of cyclin D1 coordinates cell proliferation and lipid synthesis.Frontiers in oncology · 2022Article
- CDK4: a master regulator of the cell cycle and its role in cancer.Genes & cancer · 2022Review
- The regulation of adipocyte growth in white adipose tissue.Frontiers in cell and developmental biology · 2022Review
- Obesity and hyperinsulinemia drive adipocytes to activate a cell cycle program and senesce.Nature medicine · 2021Article
- Regulation of p27 and Cdk2 Expression in Different Adipose Tissue Depots in Aging and Obesity.International journal of molecular sciences · 2021Article
- Inducible deletion of CDK4 and CDK6 - deciphering CDK4/6 inhibitor effects in the hematopoietic system.Haematologica · 2021Article
Corrections and comments
- Correction · 2022-07-01Error in Data · Error in Image · Updated to Retraction ·
- Retraction · 2023-03-15Error in Analyses · Error in Cell Lines/Tissues · Error in Data · Error in Results and/or Conclusions · Upgrade/Update of Prior Notice(s) ·
- Erratum issued
- Retracted
Authors and funding
22 authors at 7 institutions in 4 countries.
Funding
Abstract
Insulin resistance is a fundamental pathogenic factor that characterizes various metabolic disorders, including obesity and type 2 diabetes. Adipose tissue contributes to the development of obesity-related insulin resistance through increased release of fatty acids, altered adipokine secretion, and/or macrophage infiltration and cytokine release. Here, we aimed to analyze the participation of the cyclin-dependent kinase 4 (CDK4) in adipose tissue biology. We determined that white adipose tissue (WAT) from CDK4-deficient mice exhibits impaired lipogenesis and increased lipolysis. Conversely, lipolysis was decreased and lipogenesis was increased in mice expressing a mutant hyperactive form of CDK4 (CDK4(R24C)). A global kinome analysis of CDK4-deficient mice following insulin stimulation revealed that insulin signaling is impaired in these animals. We determined that insulin activates the CCND3-CDK4 complex, which in turn phosphorylates insulin receptor substrate 2 (IRS2) at serine 388, thereby creating a positive feedback loop that maintains adipocyte insulin signaling. Furthermore, we found that CCND3 expression and IRS2 serine 388 phosphorylation are increased in human obese subjects. Together, our results demonstrate that CDK4 is a major regulator of insulin signaling in WAT.
Indexed as
Identifiers
What OpenQuestion holds
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.