ArticleMolecular biology of the cell2010
Phosphorylation of p27Kip1 at Thr187 by cyclin-dependent kinase 5 modulates neural stem cell differentiation.
Article in Molecular biology of the cell, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 36 citations in OpenAlex.
- The Duality of Cdk5: A Master Regulator in Neurodevelopment and a Hijacked Oncogene in Cancer.Cells · 2025Review
- CDKN1B (p27/kip1) enhances drug-tolerant persister CTCs by restricting polyploidy following mitotic inhibitors.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- CDK5 Deficiency Does not Impair Neuronal Differentiation of Human Induced Pluripotent Stem Cells but Affects Neurite Outgrowth.Molecular neurobiology · 2025Article
- A Retrospective Tribute to Dr. Harish Pant (1938-2023) and His Seminal Work on Cyclin Dependent Kinase 5.Neurochemical research · 2024Article
- Off the Clock: the Non-canonical Roles of Cyclin-Dependent Kinases in Neural and Glioma Stem Cell Self-Renewal.Molecular neurobiology · 2022Review
- p27, The Cell Cycle and Alzheimer´s Disease.International journal of molecular sciences · 2022Review
- Divide or Commit - Revisiting the Role of Cell Cycle Regulators in Adult Hippocampal Neurogenesis.Frontiers in cell and developmental biology · 2019Review
- Phosphorylation of Pnut in the Early Stages ofG3 (Bethesda, Md.) · 2018Article
- Article
- Transient enhancement of proliferation of neural progenitors and impairment of their long-term survival in p25 transgenic mice.Oncotarget · 2016Article
- An essential role for Ink4 and Cip/Kip cell-cycle inhibitors in preventing replicative stress.Cell death and differentiation · 2016Article
- Article
- The Down syndrome-related protein kinase DYRK1A phosphorylates p27(Kip1) and Cyclin D1 and induces cell cycle exit and neuronal differentiation.Cell cycle (Georgetown, Tex.) · 2014Article
- Phosphorylation of the cryptochrome 1 C-terminal tail regulates circadian period length.The Journal of biological chemistry · 2013Article
- Cell cycle regulation during neurogenesis in the embryonic and adult brain.Stem cell reviews and reports · 2013Review
- Extra-cell cycle regulatory functions of cyclin-dependent kinases (CDK) and CDK inhibitor proteins contribute to brain development and neurological disorders.Genes to cells : devoted to molecular & cellular mechanisms · 2013Review
- High dimensional endophenotype ranking in the search for major depression risk genes.Biological psychiatry · 2012Article
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
Cyclin-dependent kinase 5 (Cdk5) plays a key role in the development of the mammalian nervous system; it phosphorylates a number of targeted proteins involved in neuronal migration during development to synaptic activity in the mature nervous system. Its role in the initial stages of neuronal commitment and differentiation of neural stem cells (NSCs), however, is poorly understood. In this study, we show that Cdk5 phosphorylation of p27(Kip1) at Thr187 is crucial to neural differentiation because 1) neurogenesis is specifically suppressed by transfection of p27(Kip1) siRNA into Cdk5(+/+) NSCs; 2) reduced neuronal differentiation in Cdk5(-/-) compared with Cdk5(+/+) NSCs; 3) Cdk5(+/+) NSCs, whose differentiation is inhibited by a nonphosphorylatable mutant, p27/Thr187A, are rescued by cotransfection of a phosphorylation-mimicking mutant, p27/Thr187D; and 4) transfection of mutant p27(Kip1) (p27/187A) into Cdk5(+/+) NSCs inhibits differentiation. These data suggest that Cdk5 regulates the neural differentiation of NSCs by phosphorylation of p27(Kip1) at theThr187 site. Additional experiments exploring the role of Ser10 phosphorylation by Cdk5 suggest that together with Thr187 phosphorylation, Ser10 phosphorylation by Cdk5 promotes neurite outgrowth as neurons differentiate. Cdk5 phosphorylation of p27(Kip1), a modular molecule, may regulate the progress of neuronal differentiation from cell cycle arrest through differentiation, neurite outgrowth, and migration.
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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.