Axin stimulates p53 functions by activation of HIPK2 kinase through multimeric complex formation | |
Rui, YN(Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong) ; Xu, Z(Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong) ; Lin, SY ; Lin SY(林舒勇) ; Li, QX ; Li QX(李勤喜) ; Rui, HL(Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong) ; Luo, W ; Zhou, HM(Department of Biological Sciences, Tsinghua University) ; Cheung, PY(Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong) ; Wu, ZG(Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong) ; Ye, ZY ; Ye ZY(叶志云) ; Li, P(Department of Biology, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong) ; Han, JH ; Han JH(韩家淮) ; Lin, SC ; Lin SC(林圣彩) | |
2004 | |
关键词 | apoptosis Axin HIPK2 p53 phosphorylation |
英文摘要 | Axin and p53 are tumor suppressors, controlling cell growth, apoptosis, and development. We show that Axin interacts with homeodomain-interacting protein kinase-2 (HIPK2), which is linked to UV-induced p53-dependent apoptosis by interacting with, and phosphorylating Ser 46 of, p53. In addition to association with p53 via HIPK2, Axin contains a separate domain that directly interacts with p53 at their physiological concentrations. Axin stimulates p53-dependent reporter transcription in 293 cells, but not in 293T, H1299, or SaOS-2 cells that are defective in p53 signaling. Axin, but not AxinDeltaHIPK2, activates HIPK2-mediated p53 phosphorylation at Ser 46, facilitating p53-dependent transcriptional activity and apoptosis. Specific knockdown of Axin by siRNA reduced UV-induced Ser-46 phosphorylation and apoptosis. Kinase-dead HIPK2 reduced Axin-induced p53-dependent transcriptional activity, indicating that Axin stimulates p53 function through HIPK2 kinase activity. Interestingly, HIPK2DeltaAxin that lacks its Axin-binding region acts as a dominant-positive form in p53 activation, suggesting that the Axin-binding region of HIPK2 is a putative auto-inhibitory domain. These results show that Axin acts as a tumor suppressor by facilitating p53 function through integration of multiple factors. |
语种 | 英语 |
出版者 | NATURE PUBLISHING GROUP |
内容类型 | 期刊论文 |
源URL | [http://dx.doi.org/doi:10.1038/sj.emboj.7600475] ![]() |
专题 | 生命科学-已发表论文 |
推荐引用方式 GB/T 7714 | Rui, YN,Xu, Z,Lin, SY,et al. Axin stimulates p53 functions by activation of HIPK2 kinase through multimeric complex formation[J],2004. |
APA | Rui, YN.,Xu, Z.,Lin, SY.,林舒勇.,Li, QX.,...&林圣彩.(2004).Axin stimulates p53 functions by activation of HIPK2 kinase through multimeric complex formation.. |
MLA | Rui, YN,et al."Axin stimulates p53 functions by activation of HIPK2 kinase through multimeric complex formation".(2004). |
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