A novel cytoplasmic substrate for cdk4 and cdk6 in normal and malignant epithelial derived cells.
Cyclins and cyclin-dependent kinases (cdk) have been identified as important regulators of cell replication. Molecular alteration in the cdk pathways appear to be important in cancer with some cyclins (eg cyclin D and E) proposed to be oncogenes and some inhibitors of cdk (eg p16) proposed to be tumor suppressor genes. In human breast carcinoma cell line MDA361 both cyclin D and E are overexpressed and cdk 4 and 6 are the predominate kinases which phosphorylate retinoblastoma protein and to a greater extent a novel 88 kDa protein. This 88 kDa protein was detected as a significant substrate in five of seven breast carcinoma cell lines, three lung carcinoma cell lines as well as in primary breast and lung epithelium. Normal human and murine T lymphocytes and established lymphoid cell lines are devoid of this protein and minimal amounts were detected in normal human fibroblast. In contrast to retinoblastoma protein, the 88 kDa protein appears to be more prevalent in the cytosolic than the nuclear subfraction. The phosphorylation of this 88 kDa protein by the G1 associated cdks suggest that this protein may represent another targeted substrate regulating the G1 phase of the cell cycle.
D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D002453:Cell Cycle / Q000502:physiology; D002467:Cell Nucleus / Q000201:enzymology; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases / Q000378:metabolism* / Q000502:physiology; D016213:Cyclins / Q000032:analysis / Q000378:metabolism; D003593:Cytoplasm / Q000201:enzymology; D004848:Epithelium / Q000201:enzymology; D016193:G1 Phase / Q000502:physiology; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology / Q000473:pathology; D008321:Mammary Glands, Animal / Q000166:cytology / Q000201:enzymology; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism* / Q000502:physiology; D010766:Phosphorylation; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000502:physiology; D011518:Proto-Oncogene Proteins; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured
D016213:Cyclins; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D017346:Protein Serine-Threonine Kinases; C495900:CDK4 protein, human; C495911:CDK6 protein, human; C495902:Cdk4 protein, mouse; C495912:Cdk6 protein, mouse; D051358:Cyclin-Dependent Kinase 4; D051361:Cyclin-Dependent Kinase 6; D018844:Cyclin-Dependent Kinases