v-Abl utilizes multiple mechanisms to drive G1/S progression in fibroblasts.
Transformation of 3T3 fibroblasts by the v-Abl tyrosine kinase replaces mitogenic and adhesion signals normally required for cell cycle progression. A 3T3 cell line conditionally transformed with v-Abl has been used to study v-Abl's effects on cell cycle in the context of either serum depletion or absence of adhesion signals. We show that E2F-dependent mRNAs, encoding proteins required for cell cycle progression, are induced by v-Abl. In addition, we identify two previously unknown targets of v-Abl signaling: (1) cyclin D1 and D2 mRNAs are induced upon v-Abl activation; and (2) the CDK inhibitor p27 is decreased upon v-Abl activation.
Coutts
M
M
Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Zou
X
X
Calame
K
K
D016475:3T3 Cells / Q000166:cytology; D000818:Animals; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002471:Cell Transformation, Neoplastic; D016895:Culture Media, Serum-Free; D019925:Cyclin A / Q000096:biosynthesis / Q000235:genetics; D019938:Cyclin D1 / Q000096:biosynthesis / Q000378:metabolism; D056742:Cyclin D2; D056743:Cyclin D3; D019927:Cyclin E / Q000096:biosynthesis / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000096:biosynthesis / Q000378:metabolism; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D005347:Fibroblasts / Q000166:cytology*; D016193:G1 Phase; D015972:Gene Expression Regulation, Neoplastic; D016313:Genes, abl; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D016374:Oncogene Proteins v-abl / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000502:physiology; D056465:Retinoblastoma-Binding Protein 1; D012264:Ribonucleotide Reductases / Q000096:biosynthesis / Q000235:genetics; D016196:S Phase; D015398:Signal Transduction; D013762:Tetrahydrofolate Dehydrogenase / Q000096:biosynthesis / Q000235:genetics; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000502:physiology*; D025521:Tumor Suppressor Proteins
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; C486196:Ccnd2 protein, mouse; C534697:Ccnd3 protein, mouse; C493961:Cdkn1b protein, mouse; D018797:Cell Cycle Proteins; D016895:Culture Media, Serum-Free; D019925:Cyclin A; D056742:Cyclin D2; D056743:Cyclin D3; D019927:Cyclin E; D016213:Cyclins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D008869:Microtubule-Associated Proteins; D016374:Oncogene Proteins v-abl; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D012264:Ribonucleotide Reductases; D013762:Tetrahydrofolate Dehydrogenase