Cell cycle-dependent regulation of phosphorylation of the human retinoblastoma gene product

Article Abstract:

Retinoblastoma is a hereditary cancer of the retina. The tumors grow rapidly and often metastasize, or migrate, to the brain and other organs. A gene known as RB1 has been identified which is associated with the tumor. RB1 is an anti-oncogene; when it is inactivated, uncontrollable cell multiplication occurs. The inactivation of RB1 and the subsequent development of cancer are also seen in other clinically-related tumors, such as osteosarcoma, a cancer of the bone, and small cell lung carcinoma and breast tumors. It is thought that the function of the protein Rb, which is coded for by the RB1 gene, is to restrict cell proliferation. The growth cycle of a cell has different phases, including resting and dividing stages. To gain insight as to how Rb functions, the synthesis and degradation of the protein was studied during the different phases of the cell cycle. It was shown that Rb is synthesized during all the phases of the cell cycle, but it contains more of the chemical phosphate when the cell is getting ready to replicate and is synthesizing another copy of the DNA, which is present in the cell. Proteins are commonly modified with phosphate, which has been shown to regulate or alter their function. When cell growth was stopped in tumor cells, the cells could no longer phosphorylate Rb. Therefore, underphosphorylated Rb may restrict cell proliferation. These findings increase the understanding of cell multiplication and what goes wrong in the uncontrolled state of proliferation that occurs in cancer. (Consumer Summary produced by Reliance Medical Information, Inc.)

Cancer research, Cancer

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Failure to phosphorylate the retinoblastoma gene product in senescent human fibroblasts

Article Abstract:

The gene that is involved in the development of retinoblastomas (RBs) (tumor of the retina of the eye) is an inhibitor of cell growth, or an anti-oncogene. The gene is inactivated or absence in RBs that lead to tumor growth. In normal cells, molecules of phosphate must be added to the RB gene product so that cells grow and division is not inhibited. Fibroblasts, a type of connective tissue cell, can only divide a certain number of times, after which they remain alive, but in a senescent state. It is thought that senescent fibroblasts contain an inhibitor that stops them from going further into the cell cycle and replicating. Fibroblasts become quiescent, or non-dividing, if deprived of growth factors. Senescent and quiescent fibroblasts contain the unphosphorylated form of RB. With the addition of growth factors, quiescent fibroblasts can phosphorylate the RB gene product and begin to divide, but senescent cells cannot. Thus, the inability to phosphorylate the RB gene product may be why senescent fibroblasts cannot divide. It is thought that cancerous cells have a factor that can override the inhibitor. Oncogenes, genes that are involved in the abnormal division of cells, can form complexes with the RB gene product, causing its inactivation, resulting in abnormal cell growth. (Consumer Summary produced by Reliance Medical Information, Inc.)

Physiological aspects, Cells (Biology), Growth, Cells, Tumor suppressor genes, Oncogenes, Fibroblasts

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Viewpoint: putting the cell cycle in order

Article Abstract:

Researchers have made important progress in understanding the alternation and completion problems of the cell cycle. Studies of the regulation of major transitions in the chromosome cycle of eukaryotes are discussed.

Cover Story, Mitosis

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