
【JMC】TEAD靶点综述 - 知乎 - 知乎专栏
转录增强缔合域(TEAD)蛋白是 Hippo河马信号通路 的下游效应子,可调节细胞增殖和干细胞功能。 TEAD无法激活转录,需要辅助激活剂(例如YAP,TAZ,VgLL和p160蛋白)的帮助。 TEAD家族的表达在许多类型的癌症中上调,包括胃癌,结肠直肠癌,乳腺癌和前列腺癌,这与患者的不良生存率相关。 因此,TEAD的药理调节剂可在癌症治疗和再生医学中找到应用。 在这篇综述中,我们介绍了带有或不带有共激活剂或抑制剂的TEADs的最新可用结构,并讨论了其配体 …
抗肿瘤药物靶标:转录增强相关结构域蛋白 (TEADs) - 知乎
Hippo通路对多种细胞或者组织信号,包括顶-底极性 (Apicobasal polarity)、力学转导 (Mechanotransduction)、细胞-细胞黏附 (Cell–cell adhesion) 和接触抑制 (Contact inhibition) 做出反应;进而调节细胞增殖、生存、竞争、干细胞维持、转移和再生。 哺乳动物的Hippo通路中,上游刺激激活 MST1/2 丝/苏氨酸蛋白激酶 (mammalian STE20-like protein kinase,与果蝇中Hippo同源);MST1/2与适配蛋白Slavador同源物1 (SAV1) 及MOB蛋白激酶1 (MOB1) 组成复合物,进 …
Motif orientation matters: Structural characterization of TEAD1 ...
2021年4月1日 · TEAD transcription factors regulate gene expression through interactions with DNA and other proteins. They are crucial for the development of eukaryotic organisms and to control the expression of genes involved mostly in cell proliferation and differentiation; however, their deregulation can lead to tumorigenesis.
Therapeutic targeting of TEAD transcription factors in cancer
2023年1月26日 · TEAD transcription factors pair with YAP and TAZ to orchestrate various transcriptional programs of cell proliferation and cell death suppression that promote cancer development. The structure of TEAD complexed with YAP/TAZ reveals several possible avenues for pharmacological modulation, making TEAD an attractive therapeutic target.
Analysis of chromatin accessibility uncovers TEAD1 as a ... - Nature
2018年10月1日 · We uncover two distinct regulatory GSC signatures, a developmentally shared/proliferative and a tumor-specific/migratory one in which TEAD1/4 motifs are uniquely overrepresented. Using ChIP-PCR, we...
Structural insights into a highly flexible zinc finger module unravel ...
2025年3月4日 · ZF1 binds to the TEAD domain of TEAD1 through hydrophobic interactions, and forms a ternary complex with TEAD1 and TEAD1-targeted DNA. ... part contains a Snail/Ggi-1 (SNAG) motif and two proline ...
Regulation of TEAD Transcription Factors in Cancer Biology
TEAD deregulation affects well-established cancer genes such as KRAS, BRAF, LKB1, NF2, and MYC, and its transcriptional output plays an important role in tumor progression, metastasis, cancer metabolism, immunity, and drug resistance. To date, TEADs have been recognized to be key transcription factors of the Hippo pathway.
The TEAD Family and Its Oncogenic Role in Promoting …
TEAD proteins are required for the participation of coactivators to transmit the signal of pathways for the downstream signaling processes. TEADs also play an important role in tumor initiation and facilitate cancer progression via activating a series of progression-inducing genes, such as CTGF, Cyr61, Myc and Gli2.
Tead transcription factors differentially regulate cortical …
2020年3月13日 · Hippo signaling regulates gene expression through Tead transcription factors (TFs). We show that Hippo transcriptional coactivators Yap1/Taz and the Teads have distinct functions during cortical...
YAP1 Exerts Its Transcriptional Control via TEAD-Mediated ... - PLOS
2015年8月21日 · We demonstrate that TEAD transcription factors mediate YAP1 chromatin-binding genome-wide, further explaining their dominant role as primary mediators of YAP1-transcriptional activity.