P27 Kip1 Nuclear Localization and Cyclin-dependent Kinase Inhibitory Activity Are Regulated by Glycogen Synthase Kinase-3 in Human Colon Cancer Cells

Overview

Journal Cell Death Differ

Specialty Cell Biology

Date 2008 Apr 15

PMID 18408738

Citations 19

Authors

Q Wang

Y Zhou

X Wang

B M Evers

Affiliations

Soon will be listed here.

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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References

Evers B, Ko T, Li J, Thompson E . Cell cycle protein suppression and p21 induction in differentiating Caco-2 cells. Am J Physiol. 1996; 271(4 Pt 1):G722-7. DOI: 10.1152/ajpgi.1996.271.4.G722. View

Zavitz K, Zipursky S . Controlling cell proliferation in differentiating tissues: genetic analysis of negative regulators of G1-->S-phase progression. Curr Opin Cell Biol. 1998; 9(6):773-81. DOI: 10.1016/s0955-0674(97)80077-4. View

Espinosa L, Ingles-Esteve J, Aguilera C, Bigas A . Phosphorylation by glycogen synthase kinase-3 beta down-regulates Notch activity, a link for Notch and Wnt pathways. J Biol Chem. 2003; 278(34):32227-35. DOI: 10.1074/jbc.M304001200. View

Phiel C, Klein P . Molecular targets of lithium action. Annu Rev Pharmacol Toxicol. 2001; 41:789-813. DOI: 10.1146/annurev.pharmtox.41.1.789. View

Forde J, Dale T . Glycogen synthase kinase 3: a key regulator of cellular fate. Cell Mol Life Sci. 2007; 64(15):1930-44. PMC: 11136264. DOI: 10.1007/s00018-007-7045-7. View

Watcharasit P, Bijur G, Zmijewski J, Song L, Zmijewska A, Chen X . Direct, activating interaction between glycogen synthase kinase-3beta and p53 after DNA damage. Proc Natl Acad Sci U S A. 2002; 99(12):7951-5. PMC: 123001. DOI: 10.1073/pnas.122062299. View

Appleman L, van Puijenbroek A, Shu K, Nadler L, Boussiotis V . CD28 costimulation mediates down-regulation of p27kip1 and cell cycle progression by activation of the PI3K/PKB signaling pathway in primary human T cells. J Immunol. 2002; 168(6):2729-36. DOI: 10.4049/jimmunol.168.6.2729. View

Dohda T, Maljukova A, Liu L, Heyman M, Grander D, Brodin D . Notch signaling induces SKP2 expression and promotes reduction of p27Kip1 in T-cell acute lymphoblastic leukemia cell lines. Exp Cell Res. 2007; 313(14):3141-52. DOI: 10.1016/j.yexcr.2007.04.027. View

Ptasznik A, Beattie G, Mally M, Cirulli V, Lopez A, Hayek A . Phosphatidylinositol 3-kinase is a negative regulator of cellular differentiation. J Cell Biol. 1997; 137(5):1127-36. PMC: 2136228. DOI: 10.1083/jcb.137.5.1127. View

10.

Diehl J, Cheng M, Roussel M, Sherr C . Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization. Genes Dev. 1998; 12(22):3499-511. PMC: 317244. DOI: 10.1101/gad.12.22.3499. View

11.

Traber P . Differentiation of intestinal epithelial cells: lessons from the study of intestine-specific gene expression. J Lab Clin Med. 1994; 123(4):467-77. View

12.

Hoeflich K, Luo J, Rubie E, Tsao M, Jin O, Woodgett J . Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation. Nature. 2000; 406(6791):86-90. DOI: 10.1038/35017574. View

13.

Auld C, Caccia C, Morrison R . Hormonal induction of adipogenesis induces Skp2 expression through PI3K and MAPK pathways. J Cell Biochem. 2006; 100(1):204-16. DOI: 10.1002/jcb.21063. View

14.

Rouet-Benzineb P, Aparicio T, Guilmeau S, Pouzet C, Descatoire V, Buyse M . Leptin counteracts sodium butyrate-induced apoptosis in human colon cancer HT-29 cells via NF-kappaB signaling. J Biol Chem. 2004; 279(16):16495-502. DOI: 10.1074/jbc.M312999200. View

15.

Jonason J, Gavrilova N, Wu M, Zhang H, Sun H . Regulation of SCF(SKP2) ubiquitin E3 ligase assembly and p27(KIP1) proteolysis by the PTEN pathway and cyclin D1. Cell Cycle. 2007; 6(8):951-61. DOI: 10.4161/cc.6.8.4104. View

16.

Jin Z, Kurosu T, Yamaguchi M, Arai A, Miura O . Hematopoietic cytokines enhance Chk1-dependent G2/M checkpoint activation by etoposide through the Akt/GSK3 pathway to inhibit apoptosis. Oncogene. 2005; 24(12):1973-81. DOI: 10.1038/sj.onc.1208408. View

17.

Tureckova J, Vojtechova M, Kucerova D, Velek J, Tuhackova Z . Sodium butyrate-mediated differentiation of colorectal cancer cells: regulation of PKCbetaII by PI 3-kinase. Int J Mol Med. 2005; 15(2):329-35. View

18.

Alao J, Stavropoulou A, Lam E, Coombes R . Role of glycogen synthase kinase 3 beta (GSK3beta) in mediating the cytotoxic effects of the histone deacetylase inhibitor trichostatin A (TSA) in MCF-7 breast cancer cells. Mol Cancer. 2006; 5:40. PMC: 1592505. DOI: 10.1186/1476-4598-5-40. View

19.

Chen J, Faller D . Histone deacetylase inhibition-mediated post-translational elevation of p27KIP1 protein levels is required for G1 arrest in fibroblasts. J Cell Physiol. 2004; 202(1):87-99. DOI: 10.1002/jcp.20094. View

20.

Surjit M, Lal S . Glycogen synthase kinase-3 phosphorylates and regulates the stability of p27kip1 protein. Cell Cycle. 2007; 6(5):580-8. DOI: 10.4161/cc.6.5.3899. View