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DAND5 encodes a member of the BMP (bone morphogenic protein) antagonist family.
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High DAND5 expression is associated with tumor growth and angiogenesis in breast cancer.
In this work, we report two patients with a DAND5 heterozygous non-synonymous variant (c.455G > A) in the functional domain of the DAND5 protein (p.R152H), a master regulator of Nodal signaling. Patient 1 presents left isomerism, ventricular septal defect with overriding aorta and pulmonary atresia, while patient 2 presents ventricular septal defect with overriding aorta, right ventricular hypertrophy
A gain-of-function cDNA screen reveals that Coco, a secreted antagonist of TGF-beta (show TGFB1 Antibodies) ligands, induces dormant breast cancer cells to undergo reactivation in the lung.
Coco binds to TGFbeta1 (show TGFB1 Antibodies) and enhances TGFbeta1 (show TGFB1 Antibodies) binding to its receptor Alk5 (show TGFBR1 Antibodies) thus acting as both an inhibitor and an enhancer of signaling, depending on the ligand it binds.
Coco required to prevent Activin (show Actbeta Antibodies) and Nodal signals in dorsal marginal side of embryo from invading the prospective ectoderm, thereby restricting endoderm- and mesoderm-inducing signals to the vegetal and marginal zones of the pre-gastrula Xenopus embryo
Data suggest that Coco acts as a critical target of flow, suggesting that symmetry is broken by flow-mediated left-asymmetric release of Nodal repression at the midline.
Coco directly inhibits derriere (show GDF3 Antibodies) and Xnr1 (show NODAL Antibodies), and with them define a posttranscriptionally regulated signaling center which is a necessary link in the signaling chain leading to an increased TGF-beta (show TGFB1 Antibodies) signal on the left side of the embryo.
Cerl2 plays an important role during heart development.
The consequent prolonged Nodal activity in the node by the absence of Cerl2 affects local Nodal expression and prolongs its expression in the lateral plate mesoderm.
Decay of Cerl2 mRNA on the left is initiated by the leftward flow and further enhanced by the operation of Wnt (show WNT2 Antibodies)-Cerl2 interlinked feedback loops.
Study shows the cilia protein Arl13b (show ARL13B Antibodies) is required for left right axis specification as its absence results in heterotaxia; the defect originates in the node where Cerl2 is not downregulated and asymmetric expression of Nodal is not maintained resulting in symmetric expression of both genes.
Cerl-2 plays a key role in restricting the Nodal signaling pathway toward the left side of the mouse embryo by preventing its activity in the right side
cCer and mouse Cerl-2 have evolved distinct regulatory mechanisms but retained a conserved function in left-right development, which is to restrict Nodal activity to the left side of the embryo.
This gene encodes a member of the BMP (bone morphogenic protein) antagonist family. Like BMPs, BMP antagonists contain cystine knots and typically form homo- and heterodimers. The CAN (cerberus and dan) subfamily of BMP antagonists, to which this gene belongs, is characterized by a C-terminal cystine knot with an eight-membered ring. The antagonistic effect of the secreted protein encoded by this gene is likely due to its direct binding to BMP proteins. As an antagonist of BMP, this gene may play a role in regulating organogenesis, body patterning, and tissue differentiation. In mouse, this protein has been shown to bind Nodal and to inhibit the Nodal signaling pathway which patterns left/right body asymmetry.
DAN domain family member 5
, DAN domain family, member 5
, cerberus 2
, cerberus-like 2
, cerberus-like protein 2
, cysteine knot superfamily 1, BMP antagonist 3
, cerberus-like 2 protein