Gli
Two transmembrane proteins are crucial for intracellular transmission of the Hh signal: the tumor suppressor membrane protein Patched (Ptch1) and the seven-transmembrane domain G-protein coupled receptor-like protein Smoothened (Smo). The activity of Smo affects the bifunctional glioma-associated oncogene transcription factors (Gli), which are transcriptional effectors of the Hh pathway. Gli proteins are members of the family of Kruppel-like factors with highly conserved Zn finger DNA-binding domains. In mammals, they are represented by three proteins: Gli1, Gli2 and Gli3. Gli1 acts principally as a transcriptional activator, whereas Gli2 and Gli3 display both activator and repressor functions. Gli proteins are extensively modified posttranslationally, and these modifications largely determine their trafficking in the cell and ultimate transcriptional output of the Hh pathway.
Among the posttranslational modifications of Gli1/2/3 are: phosphorylation, ubiquitination/proteasomal truncation, acetylation, sumoylation, methylation, and O-GlcNAcylation. In the absence of genetic or epigenetic alterations at the level of the canonical Hh pathway components, overactivation of Gli proteins may occur non-canonically via cross-talk with other signaling pathways. Among pro-tumorigenic pathways that regulate Gli proteins independently of the canonical Ptch1-Smo axis are: the mitogen-activated kinases (MAPK) cascade, the transforming growth factor beta (TGFβ) pathway, the epidermal growth factor receptor (EGFR) pathway, and the fibroblast growth factor receptor (FGFR) pathway.
References
1.Niewiadomski P, et al. Cells. 2019;8(2):147. Published 2019 Feb 11.
Among the posttranslational modifications of Gli1/2/3 are: phosphorylation, ubiquitination/proteasomal truncation, acetylation, sumoylation, methylation, and O-GlcNAcylation. In the absence of genetic or epigenetic alterations at the level of the canonical Hh pathway components, overactivation of Gli proteins may occur non-canonically via cross-talk with other signaling pathways. Among pro-tumorigenic pathways that regulate Gli proteins independently of the canonical Ptch1-Smo axis are: the mitogen-activated kinases (MAPK) cascade, the transforming growth factor beta (TGFβ) pathway, the epidermal growth factor receptor (EGFR) pathway, and the fibroblast growth factor receptor (FGFR) pathway.
References
1.Niewiadomski P, et al. Cells. 2019;8(2):147. Published 2019 Feb 11.
Wnt/Notch/Hedgehog
Gli
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Glabrescione B
产品货号 : M15505
cas no: 65893-94-9
Glabrescione B (GlaB) 是一种与 Gli1 锌指结合的小分子,通过干扰 Gli1/DNA 相互作用来损害 Gli1 活性。 -
GANT 58
产品货号 : M15435
cas no: 64048-12-0
GANT 58 (NSC 75503) 是一种有效的 Gli 拮抗剂和 Hedgehog 信号 (Hh) 抑制剂,可抑制 GLI1 诱导的转录,IC50 为 5 uM。 -
Hedgehog-IN-7d
产品货号 : M14103
cas no: 330796-24-2
Hedgehog-IN-7d 是一种有效的细胞渗透性 Hedgehog (Hh) 通路抑制剂,可抑制 Gli 转录活性,IC50 值为 70 nM。 -
JK184
产品货号 : M14026
cas no: 315703-52-7
JK184 是刺猬 (Hh) 信号通路的拮抗剂和 Gli 抑制剂。 -
FN1-8
产品货号 : M11753
cas no: 1419258-63-1
一种新型合成小分子,可有效干扰 Gli/TAF9 相互作用并下调 Gli/TAF9 依赖性转录活性(15 uM)。