NF2缺失肿瘤中Hippo信号传导失调已得到广泛研究,NF2缺失导致 LATS1/2 激酶对YAP/TAZ的磷酸化减少,导致核定位增加并提高YAP和TAZ的活性。YAP和TAZ的靶基因包括那些涉及细胞增殖、细胞死亡和细胞骨架功能的基因。我们发现,YAP或TAZ的缺失都会...
Tis相互作用导致Lats1/2蛋白的激活,导致YAP(yes相关蛋白)和与PDZ结合基序(TAZ)[136]的转录共激活因子进一步失活。YAP/TAZ的磷酸化通过与细胞质中的14.3.3蛋白复合物结合,有利于其降解或细胞质保留。由于没有merlin 中,YAP/TAZ 将在细胞核内稳...
在 DRG 和 VG 肿瘤部位,YAP 或 TAZ 的缺失显着降低了细胞增殖;尽管 YAP 或 TAZ 的缺失似乎对 VG 增殖的影响大于 DRG(图 1A-J)。 DRG 石蜡切片的染色(NF2 fl/fl -CRE-)、NF2 单空(NF2 fl/fl -CRE+)、NF2/YAP 双敲除(NF2 fl/fl YAP fl/fl -CRE+)和 NF2/TAZ双敲除 (NF2 fl/fl TAZ fl/fl...
(lats1/2)来启动yes相关蛋白1/转录共激活因子pdz结合基序(yap/taz)的降解来上调hippo通路.此外,干扰素基因刺激因子(sting)通路被merlin通过干扰素调节因子3 (irf3)相互作用正向调节,从而使rna和dna感知发生在健康细胞内. 与nf 2相关脑膜瘤的自然史 细胞和发育起源 尽管对人类脑膜发育起源的研究相对较少,但该领域的...
转录因子YAP和带有PDZ结合图案的转录辅助因子(TAZ)受Hippo信号的调节。当YAP/TAZ被转运到细胞核时,它们与DNA结合的TEAD蛋白相互作用,启动目标基因的转录。NF2突变可导致Hippo途径的功能障碍,从而导致增殖失控和分化受损。 VT3989被设计为通过占据棕榈酸酯口袋和抑制棕榈酰化来抑制TEAD/YAP的转录功能。临床前研究表明,用...
图4:使用锚定多重 PCR 的 RNA 测序揭示了 YAP1 的外显子 5 和 MAML2 的外显子 2 之间的框内融合 神经鞘瘤的致病基因突变及其正确诊断的分析及共识 神经外科肿瘤的基因解码与基因检测在 NF2 野生型神经鞘瘤中发现的致癌YAP1-MAML2融合支持这样的观点,即通过效应器YAP/TAZ的典型Hippo信号传导是神经鞘瘤发生...
(HPO2), where MAP4K1-7, a Hippo-like kinase, can phosphorylate and activate LATS1/2 and merlin48. These two signalling modules coregulate the activity of LATS1/2 kinase and YAP/TAZ but were found to differentially regulate liver size and liver cancer development in mice49. The specific ...
Neurosciences Preliminary Study on How Tumor Suppressor Nf2 Inhibits Transcriptional Coactivators Yap/Taz in the Developing Mouse Brain THE UNIVERSITY OF TENNESSEE HEALTH SCIENCE CENTER Xinwei Cao HeYuNormal brain development requires precise coordination of neural progenitor proliferation and differentiation, ...
Multiple Merlin/NF2 effector pathways including the Hippo-YAP/TAZ pathway have been identified. However, the molecular mechanisms underpinning the growth and survival of NF2-mutant tumors remain poorly understood. Using an inducible orthotopic kidney tumor model, we demonstrate that YAP/TAZ silencing is...
l, Western blot analysis of expression of YAP and TAZ in CA-46 Burkitt lymphoma cells. m, Cell death measurement of CA-46 cells treated as indicated after 24 h. All data are mean ± s.d. from n = 3 biological replicates. Source data Extended Data Fig. 8 YAP regulates ferroptosis. ...