Cell Cycle--Dependent Regulation of Phosphorylation of the Human Retinoblastoma Gene Product

• Published in: Science (American Association for the Advancement of Science) 1989-12, Vol.246 (4935), p.1300-1303
• Main Authors: Mihara, Koichiro, Cao, Xiang-Rong, Yen, Andrew, Chandler, Suzanne, Driscoll, Barbara, Murphree, A. Linn, Anne T'Ang, Fung, Yuen-Kai T.
• Format: Article
• Language: English
• Subjects: Antibodies; Biochemistry; Biological and medical sciences; Cancer; Cancer research; Cell adhesion; Cell cycle; Cell Cycle - genetics; Cell cycle, cell proliferation; Cell Division - drug effects; Cell Division - genetics; Cell growth; Cell lines; Cell physiology; DNA; Endothelial cells; Eye Neoplasms - genetics; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Neoplastic; gene products; genes; Genetics; Humans; Interphase; Interphase - genetics; Molecular and cellular biology; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Oncology, Experimental; Phosphorylation; Protein Processing, Post-Translational - drug effects; Protein Processing, Post-Translational - genetics; Rb-1; Retinoblastoma; Retinoblastoma - genetics; Tretinoin - pharmacology; Tumor Cells, Cultured; Tumors
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.2588006

The human retinoblastoma gene (RB1) encodes a protein (Rb) of 105 kilodaltons that can be phosphorylated. Analysis of Rb metabolism has shown that the protein has a half-life of more than 10 hours and is synthesized at all phases of the cell cycle. Newly synthesized Rb is not extensively phosphorylated (it is ``underphosphorylated'') in cells in the G$_{0}$ and G$_{1}$ phases but is phosphorylated at multiple sites at the G$_{1}$/S boundary and in S phase. HL-60 cells that were induced to terminally differentiate by various chemicals lost their ability to phosphorylate newly synthesized Rb at multiple sites when cell growth was arrested. These findings suggest that underphosphorylated Rb may restrict cell proliferation.