The transcription factor GLI3 is a member of the Hedgehog (Hh/HH) signaling pathway that can exist as a full length (Gli3-FL/GLI3-FL) or repressor (Gli3-R/GLI3-R) form. In response to HH activation, GLI3-FL regulates HH genes by targeting the GLI1 promoter.

Activation of Hh/GLI in cancer is most often through a non-canonical method of activation, independent of ligand binding. This review is intended to summarize our current understanding of the Hh/GLI signaling, non-canonical mechanisms of pathway activation, its implication in disease, and the current therapeutic strategies targeting this cascade.

III 型是 Gli 介导的 Hh 信号转导：(即不依赖 Smo、依赖 Gli 的 Hh 信号转导)，Gli 转录因子的激活独立于 Gli 的任何上游信号，如 Hh 配体、Ptch 和 Smo。 已经观察到多种信号级联，如 K-Ras、TGF-β，RAF-MEK-MAPK、PI3K-AKT 和 TNF-α 参与激活 Gli 活性。

2017年6月29日 · GLI3R inhibits Hh signaling and is required for response to SMO antagonist in AML. GLI3 is silenced in AML, and decitabine restores GLI3 expression and leads to modulation of Hh signaling. The Hedgehog (Hh) signaling pathway is activated in many cancers and is a promising target for therapeutic development.

2022年2月10日 · Contrary to current dogma, we find that GLI3 is inert prior to HH signaling. While GLI3 binds to most targets, loss of Gli3 does not increase target gene expression, enhancer acetylation or...

2020年4月3日 · In response to HH activation, GLI3-FL regulates HH genes by targeting the GLI1 promoter. In the absence of HH signaling, GLI3 is phosphorylated leading to its partial degradation and the generation of GLI3-R which represses HH functions. GLI3 is also involved in tissue development, immune cell development and cancer. The absence of Gli3 in mice ...

2025年1月16日 · Our study unveiled a novel role of the truncated form of Gli (t-Gli3) in advancing CRPC. Investigation into Gli3 regulation revealed a Smo-independent mechanism for its activation. Despite...

2025年1月2日 · We identified chromatin remodelling complex Hira to interact with Gli3R protein, showed that its loss-of-function changes Hh pathway activity, and examined possible mechanism behind the observed...

2024年12月25日 · GLI3 (GLI Family Zinc Finger 3) is a Protein Coding gene. Diseases associated with GLI3 include Greig Cephalopolysyndactyly Syndrome and Polydactyly, Postaxial, Type A1. Among its related pathways are Gene expression (Transcription) and Regulation of activated PAK-2p34 by proteasome mediated degradation.

In summary, we have identified TLR signaling as a novel HH-independent signaling pathway that regulates GLI3 and demonstrate that this regulation is dependent on TRIF-IRF3 signaling axis. Additionally, to our knowledge, this is the first report of the regulatory components of the TLR-GLI3 axis where IRF3 is identified as a novel transcription ...