PUBLICATION
Targeting of SET/I2PP2A oncoprotein inhibits Gli1 transcription revealing a new modulator of Hedgehog signaling
- Authors
- Serifi, I., Besta, S., Karetsou, Z., Giardoglou, P., Beis, D., Niewiadomski, P., Papamarcaki, T.
- ID
- ZDB-PUB-210708-2
- Date
- 2021
- Source
- Scientific Reports 11: 13940 (Journal)
- Registered Authors
- Papamarcaki, Thomais, Serifi, Iliana
- Keywords
- none
- MeSH Terms
-
- Animals
- CRISPR-Cas Systems/genetics
- Embryo, Nonmammalian/metabolism
- HEK293 Cells
- Hedgehog Proteins/metabolism*
- Humans
- Mice
- Morpholinos/pharmacology
- NIH 3T3 Cells
- Signal Transduction*
- Transcription, Genetic*
- Zebrafish/embryology
- Zebrafish/genetics*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Zinc Finger Protein GLI1/genetics*
- Zinc Finger Protein GLI1/metabolism
- PubMed
- 34230583 Full text @ Sci. Rep.
Citation
Serifi, I., Besta, S., Karetsou, Z., Giardoglou, P., Beis, D., Niewiadomski, P., Papamarcaki, T. (2021) Targeting of SET/I2PP2A oncoprotein inhibits Gli1 transcription revealing a new modulator of Hedgehog signaling. Scientific Reports. 11:13940.
Abstract
The Hedgehog (Hh)/Gli signaling pathway controls cell proliferation and differentiation, is critical for the development of nearly every tissue and organ in vertebrates and is also involved in tumorigenesis. In this study, we characterize the oncoprotein SET/I2PP2A as a novel regulator of Hh signaling. Our previous work has shown that the zebrafish homologs of SET are expressed during early development and localized in the ciliated organs. In the present work, we show that CRISPR/Cas9-mediated knockdown of setb gene in zebrafish embryos resulted in cyclopia, a characteristic patterning defect previously reported in Hh mutants. Consistent with these findings, targeting setb gene using CRISPR/Cas9 or a setb morpholino, reduced Gli1-dependent mCherry expression in the Hedgehog reporter zebrafish line Tg(12xGliBS:mCherry-NLS). Likewise, SET loss of function by means of pharmacological inhibition and gene knockdown prevented the increase of Gli1 expression in mammalian cells in vitro. Conversely, overexpression of SET resulted in an increase of the expression of a Gli-dependent luciferase reporter, an effect likely attributable to the relief of the Sufu-mediated inhibition of Gli1. Collectively, our data support the involvement of SET in Gli1-mediated transcription and suggest the oncoprotein SET/I2PP2A as a new modulator of Hedgehog signaling.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping