Stabilization of p53

Stable Identifier
R-HSA-69541
Type
Pathway
Species
Homo sapiens
Locations in the PathwayBrowser
Summation

Later studies pin-pointed that a single serine (Ser-15) was phosphorylated by ATM and phosphorylation of Ser-15 was rapidly-induced in IR-treated cells and this response was ATM-dependent (Canman et al, 1998; Banin et al, 1998 and Khanna et al, 1998). ATM also regulates the phosphorylation of p53 at other sites, especially Ser-20, by activating other serine/threonine kinases in response to IR (Chehab et al, 2000; Shieh et al, 2000; Hirao et al 2000). Phosphorylation of p53 at Ser-20 interferes with p53-MDM2 interaction. MDM2 is transcriptionally activated by p53 and is a negative regulator of p53 that targets it for degradation (Haupt et al, 1997; Kubbutat et al, 1997). In addition modification of MDM2 by ATM also affects p53 stabilization (Maya et al, 2001).

Literature References
PubMed ID Title Journal Year
10673501 The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites.

Shieh, SY, Ahn, J, Tamai, K, Taya, Y, Prives, C

Genes Dev 2000
10710310 DNA damage-induced activation of p53 by the checkpoint kinase Chk2.

Hirao, A, Kong, YY, Matsuoka, S, Wakeham, A, Ruland, J, Yoshida, H, Liu, D, Elledge, SJ, Mak, TW

Science 2000
10673500 Chk2/hCds1 functions as a DNA damage checkpoint in G(1) by stabilizing p53.

Chehab, NH, Malikzay, A, Appel, M, Halazonetis, TD

Genes Dev 2000
11331603 ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage.

Maya, R, Balass, M, Kim, ST, Shkedy, D, Leal, JF, Shifman, O, Moas, M, Buschmann, T, Ronai, Z, Shiloh, Y, Kastan, MB, Katzir, E, Oren, M

Genes Dev 2001
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