DAN (NBL1) specifically antagonizes BMP2 and BMP4 and modulates the actions of GDF9, BMP2, and BMP4 in the rat ovary

Biology of Reproduction
Wei-Ting HungChing-Wei Luo

Abstract

Although differential screening-selected gene aberrative in neuroblastoma (DAN, official symbol NBL1) is the founding member of the DAN subfamily of bone morphogenetic protein (BMP) antagonists, its antagonizing targets, gene regulation, and physiological functions remain unclear. Using diverse cell expression systems, we found that the generation of bioactive DAN is likely to be cell type specific. Unlike other phylogenetically close members, which are covalently linked homodimers, DAN forms a noncovalently linked homodimer during folding. Purified recombinant DAN specifically blocked signaling of BMP2 and BMP4 but not that of other ovarian-expressed transforming growth factor-beta members. Although widely distributed in many organs, DAN transcript level was periodically regulated by gonadotropins. Ovarian microdissection indicated that NBL1 (DAN) mRNA is mainly expressed in granulosa cells, where its transcript level is up-regulated by the gonadotropin-driven cAMP cascade. We further investigated the local regulation and ovarian functions of DAN. NBL1 (DAN) mRNA expression in granulosa cells was up-regulated by oocyte-derived growth differentiation factor 9 (GDF9), whereas treatment with DAN significantly reversed the inhibit...Continue Reading

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Citations

Sep 6, 2015·Cellular and Molecular Life Sciences : CMLS·Cátia L MarquesVincent Laizé
Apr 23, 2016·Biochimica Et Biophysica Acta·ShaoPeng WangQuan Zou
Oct 16, 2012·Journal of Molecular Biology·Chandramohan KattamuriThomas B Thompson
Apr 14, 2015·BioMed Research International·Sebastian López-OchoaFrancisco Arenas-Huertero
Jun 9, 2016·European Journal of Obstetrics, Gynecology, and Reproductive Biology·Yuki IkedaHiroaki Shibahara
May 9, 2014·Protein Science : a Publication of the Protein Society·Kristof Nolan, Thomas B Thompson
Aug 16, 2017·The Journal of Cell Biology·Rebecca McLennanPaul M Kulesa
Sep 17, 2020·Journal of Developmental Biology·Daniel HalloranAnja Nohe
Aug 5, 2021·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Nora E RenthalJoel N Hirschhorn

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Datasets Mentioned

BETA
BAA92265
AAC39725
AAH46632
BAC82440
AAK92484

Methods Mentioned

BETA
protein assay
electrophoresis
transfection
PCR
laser capture microdissection
enzyme-linked immunosorbent assay
glycosylation
protein folding

Software Mentioned

CLONTECH
DNASTAR
Prism5
MEGALIGN

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