2.50
Hdl Handle:
http://hdl.handle.net/10541/92852
Title:
Coupling of cell growth control and apoptosis functions of Id proteins.
Authors:
Norton, John D; Atherton, Graham T
Abstract:
The Id family of helix-loop-helix proteins function as negative regulators of cell differentiation and as positive regulators of G1 cell cycle control. We report here that enforced overexpression of the Id3 gene suppresses the colony-forming efficiency of primary rat embryo fibroblasts. Cotransfection with the antiapoptotic Bcl2 or BclXL gene alleviates this suppression and leads to cell immortalization. Consistent with this, enforced expression of Id genes in isolation was found to be a strong inducer of apoptosis in serum-deprived fibroblast cells. Id3-induced apoptosis was mediated at least in part through p53-independent mechanisms and could be efficiently rescued by Bcl2, BclXL, and the basic helix-loop-helix protein E47, which is known to oppose the functions of Id3 in vivo through the formation of stable heterodimers. Enforced overexpression of Id proteins has previously been shown to promote the cell cycle S phase in serum-deprived embryo fibroblasts (R. W. Deed, E. Hara, G. Atherton, G. Peters, and J. D. Norton, Mol. Cell. Biol. 17:6815-6821, 1997). The extent of apoptosis induced by loss- and gain-of-function Id3 mutants and by wild-type Id3 either alone or in combination with the Bcl2, BClXL, and E47 genes was invariably correlated with the relative magnitude of cell cycle S phase promotion. In addition, Id3-transfected cell populations displaying apoptosis and those in S phase were largely coincident in different experiments. These findings highlight the close coupling between the G1 progression and apoptosis functions of Id proteins and hint at a common mechanism for this family of transcriptional regulators in cell determination.
Affiliation:
CRC Department of Gene Regulation, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, United Kingdom. grgjdn@picr.cr.man.ac.uk
Citation:
Coupling of cell growth control and apoptosis functions of Id proteins. 1998, 18 (4):2371-81 Mol. Cell. Biol.
Journal:
Molecular and Cellular Biology
Issue Date:
Apr-1998
URI:
http://hdl.handle.net/10541/92852
PubMed ID:
9528806
Type:
Article
Language:
en
ISSN:
0270-7306
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorNorton, John Den
dc.contributor.authorAtherton, Graham Ten
dc.date.accessioned2010-02-24T12:52:21Z-
dc.date.available2010-02-24T12:52:21Z-
dc.date.issued1998-04-
dc.identifier.citationCoupling of cell growth control and apoptosis functions of Id proteins. 1998, 18 (4):2371-81 Mol. Cell. Biol.en
dc.identifier.issn0270-7306-
dc.identifier.pmid9528806-
dc.identifier.urihttp://hdl.handle.net/10541/92852-
dc.description.abstractThe Id family of helix-loop-helix proteins function as negative regulators of cell differentiation and as positive regulators of G1 cell cycle control. We report here that enforced overexpression of the Id3 gene suppresses the colony-forming efficiency of primary rat embryo fibroblasts. Cotransfection with the antiapoptotic Bcl2 or BclXL gene alleviates this suppression and leads to cell immortalization. Consistent with this, enforced expression of Id genes in isolation was found to be a strong inducer of apoptosis in serum-deprived fibroblast cells. Id3-induced apoptosis was mediated at least in part through p53-independent mechanisms and could be efficiently rescued by Bcl2, BclXL, and the basic helix-loop-helix protein E47, which is known to oppose the functions of Id3 in vivo through the formation of stable heterodimers. Enforced overexpression of Id proteins has previously been shown to promote the cell cycle S phase in serum-deprived embryo fibroblasts (R. W. Deed, E. Hara, G. Atherton, G. Peters, and J. D. Norton, Mol. Cell. Biol. 17:6815-6821, 1997). The extent of apoptosis induced by loss- and gain-of-function Id3 mutants and by wild-type Id3 either alone or in combination with the Bcl2, BClXL, and E47 genes was invariably correlated with the relative magnitude of cell cycle S phase promotion. In addition, Id3-transfected cell populations displaying apoptosis and those in S phase were largely coincident in different experiments. These findings highlight the close coupling between the G1 progression and apoptosis functions of Id proteins and hint at a common mechanism for this family of transcriptional regulators in cell determination.en
dc.language.isoenen
dc.subjectCancerous Cell Transformationen
dc.subjectCancer Proteinsen
dc.subject.mesh3T3 Cells-
dc.subject.meshAnimals-
dc.subject.meshApoptosis-
dc.subject.meshCell Cycle-
dc.subject.meshCell Division-
dc.subject.meshCell Transformation, Neoplastic-
dc.subject.meshCells, Cultured-
dc.subject.meshCulture Media, Serum-Free-
dc.subject.meshHelix-Loop-Helix Motifs-
dc.subject.meshHumans-
dc.subject.meshInhibitor of Differentiation Protein 1-
dc.subject.meshInhibitor of Differentiation Proteins-
dc.subject.meshMice-
dc.subject.meshNeoplasm Proteins-
dc.subject.meshProto-Oncogene Proteins c-bcl-2-
dc.subject.meshRats-
dc.subject.meshRepressor Proteins-
dc.subject.meshTranscription Factors-
dc.subject.meshTransfection-
dc.subject.meshbcl-X Protein-
dc.titleCoupling of cell growth control and apoptosis functions of Id proteins.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Gene Regulation, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, United Kingdom. grgjdn@picr.cr.man.ac.uken
dc.identifier.journalMolecular and Cellular Biologyen

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