| First Author | Li Q | Year | 2011 |
| Journal | Oncogene | Volume | 30 |
| Issue | 10 | Pages | 1194-204 |
| PubMed ID | 21057547 | Mgi Jnum | J:182380 |
| Mgi Id | MGI:5315336 | Doi | 10.1038/onc.2010.499 |
| Citation | Li Q, et al. (2011) AXIN is an essential co-activator for the promyelocytic leukemia protein in p53 activation. Oncogene 30(10):1194-204 |
| abstractText | The PML protein is best known for its role as a tumor suppressor for acute promyelocytic leukemia. Both PML and the key Wnt signaling regulator AXIN regulate p53-dependent apoptosis in response to DNA damage. However, how the two major tumor suppressors coordinate with each other is unknown, and the molecular components orchestrating the PML-induced apoptosis remain enigmatic. Here we show that AXIN interacts with PML in vivo, and further that AXIN, PML and p53 form a ternary complex. Exposure to genotoxic signals including UV and doxorubicin induces AXIN to enter into the nucleus where it colocalizes with PML in the nuclear bodies. Domain-mapping experiments revealed that the C-terminal region (aa 597-832) of AXIN is responsible for its interaction with PML. AXIN fails to activate p53 in PML(-/-) cells, and conversely, PML is unable to activate p53 in AXIN-null SNU475 cells. Consistently, knockdown with respective siRNAs revealed that AXIN and PML depend on each other to elevate p53-Ser-46 phosphorylation and to induce apoptosis after treatment with genotoxins. Moreover, we found that dominant-negative mutants of PML blocked AXIN-induced p53 activation, and that AXIN promotes PML sumoylation, a modification necessary for PML functions. Our finding has thus provided a new avenue for understanding the mechanism by which PML activates p53 and exerts its role as a tumor suppressor. |
