HIF-1α and TAZ serve as reciprocal co-activators in human breast cancer cells.
HIF-1α and TAZ serve as reciprocal co-activators in human breast cancer cells.
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HIF-1α 和 TAZ 作为人类乳腺癌细胞的相互共激活剂
DOI：
10.18632/oncotarget.4190
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发表时间：
2015-05-20
期刊：
影响因子：
--
通讯作者：
Semenza GL
中科院分区：
文献类型：
--
作者：
Xiang L;Gilkes DM;Hu H;Luo W;Bullen JW;Liang H;Semenza GL
缺氧诱导因子1α（HIF-1α）表达是肿瘤内缺氧的标志，与乳腺癌转移和患者死亡率相关。以前，我们证明了HIF-1通过增加TAZ合成和核定位来刺激TAZ的表达和活性，TAZ是Hippo信号通路的转录效应子。在这里，我们报告了HIF-1α和TAZ之间的直接蛋白质-蛋白质相互作用具有相互作用：HIF-1α刺激TAZ介导的反式激活，TAZ刺激HIF-1α介导的反式激活。TAZ表达的抑制削弱了低氧诱导HIF-1靶基因，如PDK 1，LDHA，BNIP 3和P4 HA 2对低氧的反应，而HIF-1α表达的抑制削弱了TAZ介导的CTGF启动子的反式激活。总之，这些结果补充了我们以前的发现，并建立了HIF-1α和TAZ之间的双向串扰，增加了它们在缺氧细胞中的转录活性。
Hypoxia-inducible factor 1α (HIF-1α) expression is a hallmark of intratumoral hypoxia that is associated with breast cancer metastasis and patient mortality. Previously, we demonstrated that HIF-1 stimulates the expression and activity of TAZ, which is a transcriptional effector of the Hippo signaling pathway, by increasing TAZ synthesis and nuclear localization. Here, we report that direct protein-protein interaction between HIF-1α and TAZ has reciprocal effects: HIF-1α stimulates transactivation mediated by TAZ and TAZ stimulates transactivation mediated by HIF-1α. Inhibition of TAZ expression impairs the hypoxic induction of HIF-1 target genes, such as PDK1, LDHA, BNIP3 and P4HA2 in response to hypoxia, whereas inhibition of HIF-1α expression impairs TAZ-mediated transactivation of the CTGF promoter. Taken together, these results complement our previous findings and establish bidirectional crosstalk between HIF-1α and TAZ that increases their transcriptional activities in hypoxic cells.
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影响因子：
8
作者：
Zhang, H.;Wong, C. C. L.;Wei, H.;Gilkes, D. M.;Korangath, P.;Chaturvedi, P.;Schito, L.;Chen, J.;Krishnamachary, B.;Winnard, P. T., Jr.;Raman, V.;Zhen, L.;Mitzner, W. A.;Sukumar, S.;Semenza, G. L.
通讯作者：
Semenza, G. L.
影响因子：
15.9
作者：
Chaturvedi, Pallavi;Gilkes, Daniele M.;Semenza, Gregg L.
通讯作者：
Semenza, Gregg L.
影响因子：
13.8
作者：
Semenza GL
通讯作者：
Semenza GL
DOI：
10.1073/pnas.93.23.12969
发表时间：
1996-11-12
影响因子：
11.1
作者：
Arany, Z;Huang, LE;Livingston, DM
通讯作者：
Livingston, DM
影响因子：
4.8
作者：
Baek, Jin Hyen;Liu, Ye V.;Semenza, Gregg L.
通讯作者：
Semenza, Gregg L.