A C-terminal protein-binding domain in the retinoblastoma protein regulates nuclear c-Abl tyrosine kinase in the cell cycle.
The ubiquitously expressed c-Abl tyrosine kinase is localized to the nucleus and binds to DNA. The DNA binding activity is regulated by cdc2-mediated phosphorylation, suggesting a cell cycle function for c-Abl. Here we show that the tyrosine kinase activity of nuclear c-Abl is regulated in the cell cycle through a ... specific interaction with the retinoblastoma protein (RB). A domain in the C-terminus of RB, outside of the A/B pocket, binds to the ATP-binding lobe of the c-Abl tyrosine kinase, resulting in kinase inhibition. The RB-c-Abl interaction is not affected by the viral oncoproteins that bind to RB. Hyperphosphorylation of RB correlates with release of c-Abl and activation of the tyrosine kinase in S phase cells. The nuclear c-Abl tyrosine kinase can enhance transcription, and this activity is inhibited by RB. Nuclear c-Abl is an S phase-activated tyrosine kinase that may participate directly in the regulation of transcription.
Mesh Terms:
Adenosine Triphosphate, Amino Acid Sequence, Binding Sites, Cell Cycle, Cell Nucleus, Enzyme Activation, Growth Inhibitors, Growth Substances, Humans, Molecular Sequence Data, Nuclear Proteins, Oligopeptides, Phosphorylation, Precipitin Tests, Protein Binding, Protein-Tyrosine Kinases, Proto-Oncogene Proteins c-abl, Retinoblastoma Protein, S Phase, Trans-Activators, Tumor Cells, Cultured
Adenosine Triphosphate, Amino Acid Sequence, Binding Sites, Cell Cycle, Cell Nucleus, Enzyme Activation, Growth Inhibitors, Growth Substances, Humans, Molecular Sequence Data, Nuclear Proteins, Oligopeptides, Phosphorylation, Precipitin Tests, Protein Binding, Protein-Tyrosine Kinases, Proto-Oncogene Proteins c-abl, Retinoblastoma Protein, S Phase, Trans-Activators, Tumor Cells, Cultured
Cell
Date: Nov. 19, 1993
PubMed ID: 8242749
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