New Ligand Binding Function of Human Cerberus and Role of Proteolytic Processing in Regulating Ligand-Receptor Interactions and Antagonist Activity

Journal of Molecular Biology
Senem Aykul, Erik Martinez-Hackert

Abstract

Cerberus is a key regulator of vertebrate embryogenesis. Its biological function has been studied extensively in frog and mouse embryos. Its ability to bind and antagonize the transforming growth factor-β (TGF-β) family ligand Nodal is well established. Strikingly, the molecular function of Cerberus remains poorly understood. The underlying reason is that Cerberus is a complex, multifunctional protein: It binds and inhibits multiple TGF-β family ligands, it may bind and inhibit some Wnt family members, and two different forms with distinct activities have been described. In addition, sequence homology between frog and mammalian Cerberus is low, suggesting that previous studies, which analyzed frog Cerberus function, may not accurately describe the function of mammalian Cerberus. We therefore undertook to determine the molecular activities of human Cerberus in TGF-β family signaling. Using purified proteins, surface plasmon resonance, and reporter gene assays, we discovered that human Cerberus bound and inhibited the TGF-β family ligands Activin B, BMP-6, and BMP-7, but not the frog Cerberus ligand BMP-2. Notably, full-length Cerberus successfully blocked ligand binding to type II receptors, but the short form was less effective...Continue Reading

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Citations

Jul 2, 2016·Analytical Biochemistry·Senem Aykul, Erik Martinez-Hackert
Jun 11, 2017·Cold Spring Harbor Perspectives in Biology·Joseph ZinskiMary C Mullins
Aug 12, 2020·The Biochemical Journal·Gregory R GipsonThomas B Thompson
Mar 11, 2016·The Journal of Biological Chemistry·Senem Aykul, Erik Martinez-Hackert
Sep 12, 2018·Molecular Genetics and Genomics : MGG·Xiaoyong PanYu-Dong Cai
Apr 10, 2020·Ageing Research Reviews·He-He HuYing-Yong Zhao
Aug 18, 2021·ELife·Kirsty Ml MackinlayMagdalena Zernicka-Goetz
Aug 28, 2021·International Journal of Molecular Sciences·Senem AykulErik Martinez-Hackert

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