ArticleMolecular and cellular biology2007
CDK4 and CDK6 delay senescence by kinase-dependent and p16INK4a-independent mechanisms.
Article in Molecular and cellular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 55 citations in OpenAlex.
- Iron overload induces cerebral endothelial senescence in aged mice and in primary culture in a sex-dependent manner.Aging cell · 2023Article
- The Evolving Pathways of the Efficacy of and Resistance to CDK4/6 Inhibitors in Breast Cancer.Cancers · 2023Review
- SNIP1 and PRC2 coordinate cell fates of neural progenitors during brain development.Nature communications · 2023Article
- Effects of Thyme (Antioxidants (Basel, Switzerland) · 2023Article
- Changes in the mammary gland during aging and its links with breast diseases.Acta biochimica et biophysica Sinica · 2023Review
- The old second messenger cAMP teams up with novel cell death mechanisms: potential translational therapeutical benefit for Alzheimer's disease and Parkinson's disease.Frontiers in physiology · 2023Review
- Therapeutic potential of CDK4/6 inhibitors in renal cell carcinoma.Nature reviews. Urology · 2022Review
- Exogenous melatonin prevents type 1 diabetes mellitus-induced bone loss, probably by inhibiting senescence.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2022Article
- mTOR Activity and Autophagy in Senescent Cells, a Complex Partnership.International journal of molecular sciences · 2021Review
- Article
- Senescence-associated-β-galactosidase staining following traumatic brain injury in the mouse cerebrum.PloS one · 2019Article
- The Immortal Senescence.Methods in molecular biology (Clifton, N.J.) · 2017Review
- Effect of reversine on cell cycle, apoptosis, and activation of hepatic stellate cells.Molecular and cellular biochemistry · 2016Article
- Immunoglobulin gene translocations in chronic lymphocytic leukemia: A report of 35 patients and review of the literature.Molecular and clinical oncology · 2016Article
- MiR-124 inhibits cell proliferation in breast cancer through downregulation of CDK4.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Evidence for a CDK4-dependent checkpoint in a conditional model of cellular senescence.Cell cycle (Georgetown, Tex.) · 2015Article
- Review
- D-cyclins repress apoptosis in hematopoietic cells by controlling death receptor Fas and its ligand FasL.Developmental cell · 2014Article
- MiR-506 suppresses proliferation and induces senescence by directly targeting the CDK4/6-FOXM1 axis in ovarian cancer.The Journal of pathology · 2014Article
- Signaling through cyclin D-dependent kinases.Oncogene · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Replicative senescence of human diploid fibroblasts (HDFs) is largely implemented by the cyclin-dependent kinase (CDK) inhibitors p16(INK4a) and p21(CIP1). Their accumulation results in a loss of CDK2 activity, and cells arrest with the retinoblastoma protein (pRb) in its hypophosphorylated state. It has become standard practice to bypass the effects of p16(INK4a) by overexpressing CDK4 or a variant form that is unable to bind to INK4 proteins. Although CDK4 and CDK6 and their INK4-insensitive variants can extend the life span of HDFs, they also cause a substantial increase in the levels of endogenous p16(INK4a). Here we show that CDK4 and CDK6 can extend the life span of HDFs that have inactivating mutations in both alleles of INK4a or in which INK4a levels are repressed, indicating that overexpression of CDK4/6 is not equivalent to ablation of p16(INK4a). However, catalytically inactive versions of these kinases are unable to extend the replicative life span, suggesting that the impact of ectopic CDK4/6 depends on their ability to phosphorylate as yet unidentified substrates rather than to sequester CDK inhibitors. Since p16(INK4a) deficiency, CDK4 expression, and p53 or p21(CIP1) ablation have additive effects on replicative life span, our results underscore the idea that senescence is an integrated response to diverse signals.
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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.