ArticleCell death and differentiation2008
p27 Kip1 nuclear localization and cyclin-dependent kinase inhibitory activity are regulated by glycogen synthase kinase-3 in human colon cancer cells.
Article in Cell death and differentiation, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 38 citations in OpenAlex.
- miR-181a-5p mediates the effects of BMP4 on intestinal cell proliferation and differentiation.Cell death & disease · 2025Article
- miR-27a-3p regulates intestinal cell proliferation and differentiation through Wnt/β-catenin signalling.Cell proliferation · 2025Article
- Targeting cell death pathways in intestinal ischemia-reperfusion injury: a comprehensive review.Cell death discovery · 2024Review
- Repurposing Niclosamide for Targeting Pancreatic Cancer by Inhibiting Hh/Gli Non-Canonical Axis of Gsk3β.Cancers · 2021Article
- Review
- Ketogenesis contributes to intestinal cell differentiation.Cell death and differentiation · 2017Article
- miR-422a inhibits cell proliferation in colorectal cancer by targeting AKT1 and MAPK1.Cancer cell international · 2017Article
- Histone Deacetylase Inhibitors Increase p27(Kip1) by Affecting Its Ubiquitin-Dependent Degradation through Skp2 Downregulation.Oxidative medicine and cellular longevity · 2016Article
- Examination of the molecular control of ruminal epithelial function in response to dietary restriction and subsequent compensatory growth in cattle.Journal of animal science and biotechnology · 2016Article
- Frontal Bone Insufficiency in Gsk3β Mutant Mice.PloS one · 2016Article
- NFAT5 represses canonical Wnt signaling via inhibition of β-catenin acetylation and participates in regulating intestinal cell differentiation.Cell death & disease · 2013Article
- Stat6 cooperates with Sp1 in controlling breast cancer cell proliferation by modulating the expression of p21(Cip1/WAF1) and p27 (Kip1).Cellular oncology (Dordrecht, Netherlands) · 2013Article
- Prodigiosin down-regulates SKP2 to induce p27(KIP1) stabilization and antiproliferation in human lung adenocarcinoma cells.British journal of pharmacology · 2012Article
- P27(Kip1), regulated by glycogen synthase kinase-3β, results in HMBA-induced differentiation of human gastric cancer cells.BMC cancer · 2011Article
- Nuclear factor of activated T cells (NFAT) signaling regulates PTEN expression and intestinal cell differentiation.Molecular biology of the cell · 2011Article
- Article
- Constitutive activation of glycogen synthase kinase-3beta correlates with better prognosis and cyclin-dependent kinase inhibitors in human gastric cancer.BMC gastroenterology · 2010Article
- Suppression of neurotensin receptor type 1 expression and function by histone deacetylase inhibitors in human colorectal cancers.Molecular cancer therapeutics · 2010Article
- Apigenin induces apoptosis via downregulation of S-phase kinase-associated protein 2-mediated induction of p27Kip1 in primary effusion lymphoma cells.Cell proliferation · 2010Article
- Nuclear targeting of 6-phosphofructo-2-kinase (PFKFB3) increases proliferation via cyclin-dependent kinases.The Journal of biological chemistry · 2009Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The cellular mechanisms regulating intestinal differentiation are poorly understood. Sodium butyrate (NaBT), a short-chain fatty acid, increases p27 Kip1 expression and induces cell cycle arrest associated with intestinal cell differentiation. Here, we show that treatment of intestinal-derived cells with NaBT induced G0/G1 arrest and intestinal alkaline phosphatase, a marker of differentiation, activity and mRNA expression; this induction was attenuated by inhibition of glycogen synthase kinase-3 (GSK-3). Moreover, treatment with NaBT increased the nuclear, but not the cytosolic, expression and activity of GSK-3beta. NaBT decreased cyclin-dependent kinase CDK2 activity and induced p27 Kip1 expression; inhibition of GSK-3 rescued NaBT-inhibited CDK2 activity and blocked NaBT-induced p27 Kip1 expression in the nucleus but not in the cytoplasm. In addition, we demonstrate that NaBT decreased the expression of S-phase kinase-associated protein 2 (Skp2), and this decrease was attenuated by GSK-3 inhibition. Furthermore, NaBT increased p27 Kip1 binding to CDK2, which was completely abolished by GSK-3 inhibition. Overexpression of an active form of GSK-3beta reduced Skp2 expression, increased p27 Kip1 in the nucleus and increased p27 Kip1 binding to CDK2. Our results suggest that GSK-3 not only regulates nuclear p27 Kip1 expression through the downregulation of nuclear Skp2 expression but also functions to regulate p27 Kip1 assembly with CDK2, thereby playing a critical role in the G0/G1 arrest associated with intestinal cell differentiation.
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