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).
Hirao, A, Elledge, SJ, Mak, TW, Yoshida, H, Liu, D, Matsuoka, S, Wakeham, A, Ruland, J, Kong, YY
Tamai, K, Taya, Y, Ahn, J, Prives, C, Shieh, SY
Appel, M, Halazonetis, TD, Chehab, NH, Malikzay, A
Shiloh, Y, Kastan, MB, Buschmann, T, Ronai, Z, Shifman, O, Moas, M, Shkedy, D, Leal, JF, Balass, M, Kim, ST, Maya, R, Katzir, E, Oren, M
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