Universität zu Köln

Ozalp, Ozgun ORCID: 0000-0002-4873-8069, Cark, Ozge, Azbazdar, Yagmur, Haykir, Betul, Cucun, Gokhan, Kucukaylak, Ismail, Alkan-Yesilyurt, Gozde, Sezgin, Erdinc ORCID: 0000-0002-4915-388X and Ozhan, Gunes ORCID: 0000-0002-4806-5917 (2021). Nradd Acts as a Negative Feedback Regulator of Wnt/beta-Catenin Signaling and Promotes Apoptosis. Biomolecules, 11 (1). BASEL: MDPI. ISSN 2218-273X

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Abstract

Wnt/beta-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 (p75(NTR)), as a negative regulator of Wnt/beta-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/beta-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/beta-catenin signaling during development.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ozalp, Ozgun UNSPECIFIED orcid.org/0000-0002-4873-8069 UNSPECIFIED Cark, Ozge UNSPECIFIED UNSPECIFIED UNSPECIFIED Azbazdar, Yagmur UNSPECIFIED UNSPECIFIED UNSPECIFIED Haykir, Betul UNSPECIFIED UNSPECIFIED UNSPECIFIED Cucun, Gokhan UNSPECIFIED UNSPECIFIED UNSPECIFIED Kucukaylak, Ismail UNSPECIFIED UNSPECIFIED UNSPECIFIED Alkan-Yesilyurt, Gozde UNSPECIFIED UNSPECIFIED UNSPECIFIED Sezgin, Erdinc UNSPECIFIED orcid.org/0000-0002-4915-388X UNSPECIFIED Ozhan, Gunes UNSPECIFIED orcid.org/0000-0002-4806-5917 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-591873
DOI:	10.3390/biom11010100
Journal or Publication Title:	Biomolecules
Volume:	11
Number:	1
Date:	2021
Publisher:	MDPI
Place of Publication:	BASEL
ISSN:	2218-273X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language Biochemistry & Molecular Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/59187