ID2 promotes the expansion and survival of growth-arrested pancreatic beta cells.
Inhibitors of DNA binding proteins (Ids) are implicated in the control of proliferation and differentiation. Herein, we tested the hypothesis that Id2 could stimulate proliferation and survival in differentiated pancreatic beta cells. We showed that Id2-enhanced proliferation of a growth-arrested pancreatic beta cell line (BTC-tet). This was mediated by the Rb pathway, as shown by an E2F1-driven reporter assay and Western immunoblot of phosphorylated Rb protein. Id2 also induced expression of Bcl-2, accompanied by a significant reduction of critical mediators of cytokine stimulation, including p38 MAPK and NFkappaB, as well as apoptosis markers, caspase-3 and Annexin-V. Overall, our data suggest that Id2 enhances proliferation and survival of growth-arrested BTC-tet cells.
Hua
Hong
H
Department of Immunology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., IMM-23, La Jolla, CA 92037, USA.
Sarvetnick
Nora
N
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival; D050687:E2F1 Transcription Factor / Q000378:metabolism; D051797:Inhibitor of Differentiation Protein 2 / Q000235:genetics / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D017304:Annexin A5; D050687:E2F1 Transcription Factor; C493754:E2f1 protein, mouse; C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D016160:Retinoblastoma Protein; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3