GSK-3 Represses Growth Factor-inducible Genes by Inhibiting NF-κB in Quiescent Cells

Abstract

GSK-3 is active in the absence of growth factor stimulation and generally acts to induce apoptosis or inhibit cell proliferation. We previously identified a subset of growth factor-inducible genes that can also be induced in

GSK-3α and GSK-3β Proteins Are Involved in Early Stages of Chondrocyte Differentiation with Functional Redundancy through RelA Protein Phosphorylation

“…In most cells, GSK-3 appears to stimulate the RelA activity via phosphorylation rather than the proteasome-dependent mechanism (10,(33)(34)(35). Contrarily, GSK-3 causes inhibition of the NF-B signal in neuronal and epithelial cells, mainly through suppression of IB phosphorylation by IKK (36,37). Hence, GSK-3 may play variable roles through distinct mechanisms in the regulation of NF-B depending on cell types and conditions.…”

The E-box Binding Factors Max/Mnt, MITF, and USF1 Act Coordinately with FoxO to Regulate Expression of Proapoptotic and Cell Cycle Control Genes by Phosphatidylinositol 3-Kinase/Akt/Glycogen Synthase Kinase 3 Signaling

“…RNA Interference-siRNA transfections were performed as described (28), using predesigned siRNAs against Myc (Ambion, S9130), Max (Ambion, S224030), Mnt (Ambion, s8904), MITF (Ambion, S8791), USF1 (Ambion, S14717), FoxO3a (Ambion, S5260), GSK3␤ (Ambion, S6241), ATROGIN-1 (Ambion, s41718), CCNG2 (Ambion, s2533), TXNIP (Ambion, s20880), or a nonspecific negative control (Ambion, 4390843). Cells were transfected with 5-20 nM siRNAs, optimized for the individual target.…”

Insulin-Like Growth Factor 1 Receptor and p38 Mitogen-Activated Protein Kinase Signals Inversely Regulate Signal Transducer and Activator of Transcription 3 Activity to Control Human Dental Pulp Stem Cell Quiescence, Propagation, and Differentiation

“…7) that explains how IGF-1R and p38 MAPK signaling pathways may interact to regulate DPSC. In building the model, we assumed that adult human DPSCs, like ESCs [80,83], self-renew and generate undifferentiated progeny due to the inactivation of GSK3 and the increased activity of STAT3 transcription factor. We also assumed that the p38 MAPK signaling pathway represses the STAT3 activity not by repressing all the functions of IGF-1R but, rather, by specifically repressing the function of its downstream STAT3-activating substrate, most likely JAK [32,41,42], which has recently been shown to stimulate odontoblasts proliferation and to inhibit odontoblasts differentiation [75].…”