Signaling by ABL oncogenes through cyclin D1.
Oncogenic signals induce cellular proliferation by deregulating the cell division cycle. Cyclin D1, a regulator of G1-phase progression, acts synergistically with ABL oncogenes in transforming fibroblasts and hematopoietic cells in culture. Synergy with v-Abl depended on a motif in cyclin D1 that mediates its binding to the retinoblastoma protein, suggesting that ABL oncogenes in part mediate their mitogenic effects via a retinoblastoma protein-dependent pathway. Overexpression of cyclin D1, but not cyclin E, rescued a signaling-defective src-homology 2 (SH2) domain mutant of BCR-ABL for transformation of cells in culture and malignant tumor formation in vivo. These results demonstrate that cyclin D1 can provide essential signals for malignant transformation in concert with an activated tyrosine kinase.
Afar
D E
DE
Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90095, USA.
McLaughlin
J
J
Sherr
C J
CJ
Witte
O N
ON
Roussel
M F
MF
D000818:Animals; D001854:Bone Marrow Cells; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D019938:Cyclin D1; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D016313:Genes, abl; D007942:Leukemia, Experimental / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011994:Recombinant Proteins; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*; D018909:src Homology Domains
D016213:Cyclins; D015513:Oncogene Proteins; D011994:Recombinant Proteins; D016160:Retinoblastoma Protein; D019938:Cyclin D1; D016044:Fusion Proteins, bcr-abl