AXIN is an essential co-activator for the promyelocytic leukemia protein in p53 activation

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	AXIN is an essential co-activator for the promyelocytic leukemia protein in p53 activation
	Li, Q. ; He, Y. ; Wei, L. ; Wu, X. ; Wu, D. ; Lin, S. ; Wang, Z. ; Ye, Z. ; Lin, S. C. ; Lin SC(林圣彩)
刊名	http://dx.doi.org/10.1038/onc.2010.499
	2011-03
关键词	NUCLEAR-BODY FORMATION TUMOR-SUPPRESSOR DNA-DAMAGE P53-DEPENDENT APOPTOSIS RAR-ALPHA PML HIPK2 GENE PHOSPHORYLATION IDENTIFICATION
英文摘要	MOST [2009CB522200, 2006AA02A303, 2007CB914602]; National Natural Science Foundation of China [30730025, 30921005, 30500273, 30770454, 30970613]; Natural Science Foundation of Fujian Province [2008J0109, 2009J06021]; program for NCET; 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. Oncogene (2011) 30, 1194-1204; doi:10.1038/onc.2010.499; published online 8 November 2010
语种	英语
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/65322]
专题	生命科学－已发表论文
推荐引用方式 GB/T 7714	Li, Q.,He, Y.,Wei, L.,et al. AXIN is an essential co-activator for the promyelocytic leukemia protein in p53 activation[J]. http://dx.doi.org/10.1038/onc.2010.499,2011.
APA	Li, Q..,He, Y..,Wei, L..,Wu, X..,Wu, D..,...&林圣彩.(2011).AXIN is an essential co-activator for the promyelocytic leukemia protein in p53 activation.http://dx.doi.org/10.1038/onc.2010.499.
MLA	Li, Q.,et al."AXIN is an essential co-activator for the promyelocytic leukemia protein in p53 activation".http://dx.doi.org/10.1038/onc.2010.499 (2011).