PUBLICATION
Nradd Acts as a Negative Feedback Regulator of Wnt/β-Catenin Signaling and Promotes Apoptosis
- Authors
- Ozalp, O., Cark, O., Azbazdar, Y., Haykir, B., Cucun, G., Kucukaylak, I., Alkan-Yesilyurt, G., Sezgin, E., Ozhan, G.
- ID
- ZDB-PUB-210121-4
- Date
- 2021
- Source
- Biomolecules 11(1): (Journal)
- Registered Authors
- Azbazdar, Yagmur, Cucun, Gokhan, Haykir, Betül, Özhan, Günes
- Keywords
- Nradd, Wnt/β-catenin signaling, apoptosis, death receptor, p75 neurotrophin receptor
- MeSH Terms
-
- Animals
- Apoptosis*/genetics
- Cell Line
- Cell Membrane/metabolism
- Ectoderm/embryology
- Ectoderm/metabolism
- Embryonic Development/genetics
- Feedback, Physiological*
- Gene Expression Regulation, Developmental
- Humans
- Mesoderm/embryology
- Mesoderm/metabolism
- Protein Binding
- Transcription, Genetic
- Wnt Signaling Pathway*/genetics
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 33466728 Full text @ Biomolecules
Citation
Ozalp, O., Cark, O., Azbazdar, Y., Haykir, B., Cucun, G., Kucukaylak, I., Alkan-Yesilyurt, G., Sezgin, E., Ozhan, G. (2021) Nradd Acts as a Negative Feedback Regulator of Wnt/β-Catenin Signaling and Promotes Apoptosis. Biomolecules. 11(1):.
Abstract
Wnt/β-catenin signaling controls many biological processes for the generation and sustainability of proper tissue size, organization and function during development and homeostasis. Consequently, mutations in the Wnt pathway components and modulators cause diseases, including genetic disorders and cancers. Targeted treatment of pathway-associated diseases entails detailed understanding of the regulatory mechanisms that fine-tune Wnt signaling. Here, we identify the neurotrophin receptor-associated death domain (Nradd), a homolog of p75 neurotrophin receptor (p75NTR), as a negative regulator of Wnt/β-catenin signaling in zebrafish embryos and in mammalian cells. Nradd significantly suppresses Wnt8-mediated patterning of the mesoderm and neuroectoderm during zebrafish gastrulation. Nradd is localized at the plasma membrane, physically interacts with the Wnt receptor complex and enhances apoptosis in cooperation with Wnt/β-catenin signaling. Our functional analyses indicate that the N-glycosylated N-terminus and the death domain-containing C-terminus regions are necessary for both the inhibition of Wnt signaling and apoptosis. Finally, Nradd can induce apoptosis in mammalian cells. Thus, Nradd regulates cell death as a modifier of Wnt/β-catenin signaling during development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping