GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:17380128

From GONUTS
Jump to: navigation, search
Citation

Inoue, Y, Kitagawa, M and Taya, Y (2007) Phosphorylation of pRB at Ser612 by Chk1/2 leads to a complex between pRB and E2F-1 after DNA damage. EMBO J. 26:2083-93

Abstract

The retinoblastoma tumor suppressor protein (pRB) plays a critical role in the control of cell proliferation and in the DNA damage checkpoints. pRB inhibits cell cycle progression through interactions with the E2F family of transcription factors. Here, we report that DNA damage induced not only the dephosphorylation of pRB at Cdk phosphorylation sites and the binding of pRB to E2F-1, but also the phosphorylation of pRB at Ser612. Phosphorylation of pRB at Ser612 enhanced the formation of a complex between pRB and E2F-1. Substitution of Ser612 with Ala decreased pRB-E2F-1 binding and the transcriptional repression activity. Until now, Ser612 of pRB has been thought to be phosphorylated by Cdk2. However, the phosphorylation of pRB at Ser612 was conducted by Chk1/2 after DNA damage, and inhibition of ATM-Chk1/2 activity suppressed the phosphorylation of Ser612 and the binding of pRB to E2F-1. These results suggest that Ser612 is phosphorylated by Chk1/2 after DNA damage, leading to the formation of pRB-E2F-1. This is the first report that pRB is phosphorylated in vivo by a kinase other than Cdk.

Links

PubMed PMC1852778 Online version:10.1038/sj.emboj.7601652

Keywords

Ataxia Telangiectasia Mutated Proteins; Cell Cycle Proteins/metabolism; Cell Line, Tumor; Checkpoint Kinase 2; Chromatography, Gel; DNA Damage; DNA Primers; DNA-Binding Proteins/metabolism; E2F1 Transcription Factor/metabolism; Humans; Phosphorylation; Protein Kinases/metabolism; Protein-Serine-Threonine Kinases/metabolism; RNA Interference; Retinoblastoma Protein/metabolism; Serine/metabolism; Signal Transduction/physiology; Tumor Suppressor Proteins/metabolism

Significance

Annotations

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

HUMAN:E2F3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P06400

F

Seeded From UniProt

complete

HUMAN:CHK1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P06400

F

Seeded From UniProt

complete

HUMAN:CHK2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P06400

F

Seeded From UniProt

complete

HUMAN:RB

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q16539

F

Seeded From UniProt

complete

HUMAN:RB

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q14209

F

Seeded From UniProt

complete

HUMAN:RB

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q01094

F

Seeded From UniProt

complete

HUMAN:RB

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O96017

F

Seeded From UniProt

complete

HUMAN:RB

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O14757

F

Seeded From UniProt

complete

HUMAN:RB

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O00716

F

Seeded From UniProt

complete

HUMAN:E2F1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P06400

F

Seeded From UniProt

complete

HUMAN:E2F2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P06400

F

Seeded From UniProt

complete

HUMAN:MK14

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P06400

F

Seeded From UniProt

complete

Notes

See also

References

See Help:References for how to manage references in GONUTS.