| Autor: |
Qinxi Li, Shuyong Lin, Xuan Wang, Guili Lian, Zailian Lu, Huiling Guo, Ka Ruan, Yanhai Wang, Zhiyun Ye, Jiahuai Han, Sheng-Cai Lin |
| Předmět: |
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| Zdroj: |
Nature Cell Biology; Sep2009, Vol. 11 Issue 9, p1128-1134, 7p, 6 Color Photographs, 2 Black and White Photographs, 3 Diagrams, 5 Graphs |
| Abstrakt: |
Cells can undergo either cell-cycle arrest or apoptosis after genotoxic stress, based on p53 activity. Here we show that cellular fate commitment depends on Axin forming distinct complexes with Pirh2, Tip60, HIPK2 and p53. In cells treated with sublethal doses of ultra-violet (UV) radiation or doxorubicin (Dox), Pirh2 abrogates Axin-induced p53 phosphorylation at Ser 46 catalysed by HIPK2, by competing with HIPK2 for binding to Axin. However, on lethal treatment, Tip60 interacts with Axin and abrogates Pirh2–Axin binding, forming an Axin–Tip60–HIPK2–p53 complex that allows maximal p53 activation to trigger apoptosis. We also provide evidence that the ATM/ATR pathway mediates the Axin–Tip60 complex assembly. An axin mutation promotes carcinogenesis in AxinFu/+ (Axin-Fused) mice, consistent with a dominant-negative role for AxinFu in p53 activation. Thus, Axin is a critical determinant in p53-dependent tumour suppression in which Pirh2 and Tip60 have different roles in triggering cell-cycle arrest or apoptosis depending on the severity of genotoxic stress. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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