Reactome | CHEK2 phosphorylates TP53

CHEK2 phosphorylates TP53

Stable Identifier

R-HSA-69685

Type

Reaction [transition]

Species

Homo sapiens

Compartment

nucleoplasm

Synonyms

Phosphorylation of p53 by ATM-activated Chk2

ReviewStatus

5/5

Locations in the PathwayBrowser

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Cell Cycle (Homo sapiens)

- Cell Cycle Checkpoints (Homo sapiens)
  - G1/S DNA Damage Checkpoints (Homo sapiens)
    - p53-Dependent G1/S DNA damage checkpoint (Homo sapiens)
      - p53-Dependent G1 DNA Damage Response (Homo sapiens)
        
        Stabilization of p53 (Homo sapiens)
        
        CHEK2 phosphorylates TP53 (Homo sapiens)

Gene expression (Transcription) (Homo sapiens)

- RNA Polymerase II Transcription (Homo sapiens)
  - Generic Transcription Pathway (Homo sapiens)
    - Transcriptional Regulation by TP53 (Homo sapiens)
      - Regulation of TP53 Activity (Homo sapiens)
        
        Regulation of TP53 Activity through Phosphorylation (Homo sapiens)
        
        CHEK2 phosphorylates TP53 (Homo sapiens)

General

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CHEK2 (Chk2) phosphorylates TP53 (p53) at serine residue S20 (Hirao et al. 2000, Shieh et al. 2000, Chehab et al. 2000). Phosphorylation of TP53 at serine residue S20 is necessary for DNA damage-induced TP53 stabilization as it compromises the interaction of TP53 with the ubiquitin ligase MDM2 (Chehab et al. 1999, Chehab et al. 2000). S20 phosphorylation is also required for the induction of TP53-dependent transcripts in response to DNA damage (Hirao et al. 2000).

Literature References

PubMed ID	Title	Journal	Year
10673500	Chk2/hCds1 functions as a DNA damage checkpoint in G(1) by stabilizing p53. Appel, M, Halazonetis, TD, Chehab, NH, Malikzay, A	Genes Dev	2000
10570149	Phosphorylation of Ser-20 mediates stabilization of human p53 in response to DNA damage Halazonetis, TD, Malikzay, A, Stavridi, ES, Chehab, NH	Proc. Natl. Acad. Sci. U.S.A.	1999
10673501	The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites. Tamai, K, Taya, Y, Ahn, J, Prives, C, Shieh, SY	Genes Dev	2000
10710310	DNA damage-induced activation of p53 by the checkpoint kinase Chk2. Hirao, A, Elledge, SJ, Mak, TW, Yoshida, H, Liu, D, Matsuoka, S, Wakeham, A, Ruland, J, Kong, YY	Science	2000