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PMID:8242749

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Citation

Welch, PJ and Wang, JY (1993) A C-terminal protein-binding domain in the retinoblastoma protein regulates nuclear c-Abl tyrosine kinase in the cell cycle. Cell 75:779-90

Abstract

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.

Links

PubMed

Keywords

Adenosine Triphosphate/metabolism; Amino Acid Sequence; Binding Sites; Cell Cycle; Cell Nucleus/enzymology; Enzyme Activation; Growth Inhibitors/physiology; Growth Substances/physiology; Humans; Molecular Sequence Data; Nuclear Proteins/metabolism; Oligopeptides/chemistry; Phosphorylation; Precipitin Tests; Protein Binding; Protein-Tyrosine Kinases/metabolism; Proto-Oncogene Proteins c-abl/metabolism; Retinoblastoma Protein/chemistry; Retinoblastoma Protein/metabolism; S Phase; Trans-Activators; Tumor Cells, Cultured

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:ABL1

enables

GO:0003677: DNA binding

ECO:0000303: author statement without traceable support used in manual assertion

F

Seeded From UniProt

complete

HUMAN:ABL1

part_of

GO:0005634: nucleus

ECO:0000303: author statement without traceable support used in manual assertion

C

Seeded From UniProt

complete

HUMAN:ABL1

involved_in

GO:0006464: cellular protein modification process

ECO:0000303: author statement without traceable support used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ABL1

involved_in

GO:0006355: regulation of transcription, DNA-templated

ECO:0000304: author statement supported by traceable reference used in manual assertion

P

Seeded From UniProt

complete


See also

References

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