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).
Shieh, SY, Ahn, J, Tamai, K, Taya, Y, Prives, C
Hirao, A, Kong, YY, Matsuoka, S, Wakeham, A, Ruland, J, Yoshida, H, Liu, D, Elledge, SJ, Mak, TW
Chehab, NH, Malikzay, A, Appel, M, Halazonetis, TD
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
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