scholarly journals Glucocorticoids Inhibit Cell Cycle Progression in Differentiating Osteoblasts via Glycogen Synthase Kinase-3β

2002 ◽  
Vol 277 (20) ◽  
pp. 18191-18197 ◽  
Author(s):  
Elisheva Smith ◽  
Gerhard A. Coetzee ◽  
Baruch Frenkel
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3Β ◽  
Cycle Progression ◽  
Inhibit Cell Cycle Progression

scholarly journals Laforin Negatively Regulates Cell Cycle Progression through Glycogen Synthase Kinase 3β-Dependent Mechanisms

2008 ◽  
Vol 28 (23) ◽  
pp. 7236-7244 ◽  
Author(s):  
Runhua Liu ◽  
Lizhong Wang ◽  
Chong Chen ◽  
Yan Liu ◽  
Penghui Zhou ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Growth ◽  
Cyclin D1 ◽  
Tumor Suppression ◽  
Cell Cycle Progression ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3Β ◽  
Cycle Progression ◽  
Gsk 3Β

ABSTRACT Glycogen synthase kinase 3β (GSK-3β) represses cell cycle progression by directly phosphorylating cyclin D1 and indirectly regulating cyclin D1 transcription by inhibiting Wnt signaling. Recently, we reported that the Epm2a-encoded laforin is a GSK-3β phosphatase and a tumor suppressor. The cellular mechanism for its tumor suppression remains unknown. Using ex vivo thymocytes and primary embryonic fibroblasts from Epm2a −/− mice, we show here a general function of laforin in the cell cycle regulation and repression of cyclin D1 expression. Moreover, targeted mutation of Epm2a increased the phosphorylation of Ser9 on GSK-3β while having no effect on the phosphorylation of Ser21 on GSK-3α. In the GSK-3β+/+ but not the GSK-3β−/− cells, Epm2a small interfering RNA significantly enhanced cell growth. Consistent with an increased level of cyclin D1, the phosphorylation of retinoblastoma protein (Rb) and the levels of Rb-E2F-regulated genes cyclin A, cyclin E, MCM3, and PCNA are also elevated. Inhibitors of GSK-3β selectively increased the cell growth of Epm2a +/+ but not of Epm2a −/− cells. Taken together, our data demonstrate that laforin is a selective phosphatase for GSK-3β and regulates cell cycle progression by GSK-3β-dependent mechanisms. These data provide a cellular basis for the tumor suppression activity of laforin.

scholarly journals Glycogen Synthase Kinase 3 Phosphorylates RBL2/p130 during Quiescence

2004 ◽  
Vol 24 (20) ◽  
pp. 8970-8980 ◽  
Author(s):  
Larisa Litovchick ◽  
Anton Chestukhin ◽  
James A. DeCaprio
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Glycogen Synthase ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Growth Factor Signaling ◽  
Cycle Progression ◽  
Pocket Proteins ◽  
Cyclin Dependent Kinases ◽  
The Stability

ABSTRACT Phosphorylation of the retinoblastoma-related or pocket proteins RB1/pRb, RBL1/p107, and RBL2/p130 regulates cell cycle progression and exit. While all pocket proteins are phosphorylated by cyclin-dependent kinases (CDKs) during the G1/S-phase transition, p130 is also specifically phosphorylated in G0-arrested cells. We have previously identified several phosphorylated residues that match the consensus site for glycogen synthase kinase 3 (GSK3) in the G0 form of p130. Using small-molecule inhibitors of GSK3, site-specific mutants of p130, and phospho-specific antibodies, we demonstrate here that GSK3 phosphorylates p130 during G0. Phosphorylation of p130 by GSK3 contributes to the stability of p130 but does not affect its ability to interact with E2F4 or cyclins. Regulation of p130 by GSK3 provides a novel link between growth factor signaling and regulation of the cell cycle progression and exit.

scholarly journals Cyclin G2, a novel target of sulindac to inhibit cell cycle progression in colorectal cancer

2020 ◽  
Author(s):  
Hongyou Zhao ◽  
Bin Yi ◽  
Zhipin Liang ◽  
Ches’Nique Phillips ◽  
Hui-Yi Lin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Inhibit Cell Cycle Progression ◽  
Cyclin G2 ◽  
Novel Target

Newly identified structurally disparate modulators of osmosensitive taurine efflux inhibit cell cycle progression

2003 ◽  
Vol 474 (2-3) ◽  
pp. 185-193 ◽  
Author(s):  
Mark J. Belsey ◽  
Steven J. Culliford ◽  
Richard M. Morley ◽  
Harry J. Witchel ◽  
Roland Z. Kozlowski
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Inhibit Cell Cycle Progression ◽  
Taurine Efflux

scholarly journals Insulin-Induced Cell Cycle Progression Is Impaired in Chinese Hamster Ovary Cells Overexpressing Insulin Receptor Substrate-3

Endocrinology ◽  
2004 ◽  
Vol 145 (12) ◽  
pp. 5862-5874 ◽  
Author(s):  
Yasushi Kaburagi ◽  
Ryo Yamashita ◽  
Yuzuru Ito ◽  
Hitoshi Okochi ◽  
Ritsuko Yamamoto-Honda ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Insulin Receptor ◽  
Cyclin D1 ◽  
Cell Cycle Progression ◽  
Glycogen Synthase ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Glycogen Synthase Kinase 3 ◽  
Cycle Progression ◽  
Ovary Cells

Abstract To analyze the roles of insulin receptor substrate (IRS) proteins in insulin-stimulated cell cycle progression, we examined the functions of rat IRS-1 and IRS-3 in Chinese hamster ovary cells overexpressing the human insulin receptor. In this type of cell overexpressing IRS-1 or IRS-3, we showed that: 1) overexpression of IRS-3, but not IRS-1, suppressed the G1/S transition induced by insulin; 2) IRS-3 was more preferentially localized to the nucleus than IRS-1; 3) phosphorylation of glycogen synthase kinase 3 and MAPK/ERK was unaffected by IRS-3 overexpression, whereas that of protein kinase B was enhanced by either IRS; 4) overexpressed IRS-3 suppressed cyclin D1 expression in response to insulin; 5) among the signaling molecules regulating cyclin D1 expression, activation of the small G protein Ral was unchanged, whereas insulin-induced gene expression of c-myc, a critical component for growth control and cell cycle progression, was suppressed by overexpressed IRS-3; and 6) insulin-induced expression of p21, a cyclin-dependent kinase inhibitor, was decreased by overexpressed IRS-3. These findings imply that: 1) IRS-3 may play a unique role in mitogenesis by inhibiting insulin-stimulated cell cycle progression via a decrease in cyclin D1 and p21 expressions as well as suppression of c-myc mRNA induction in a manner independent of the activation of MAPK, protein kinase B, glycogen synthase kinase 3 and Ral; and 2) the interaction of IRS-3 with nuclear proteins may be involved in this process.

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