Tankyrase Loses Its Grip on SH3BP2 in Cherubism
نویسندگان
چکیده
Cherubism, a case of bone remodeling gone haywire, is associated with mutations in the adaptor protein SH3BP2. Two papers in this issue of Cell (Guettler et al. and Levaot et al.) demonstrate that these mutations disrupt the interaction between SH3BP2 and Tankyrase and describe rules for substrate recognition by this poly(ADP-ribose) polymerase. Establishing such rules paves the way to identifying all Tankyrase-regulated pathways in cells.
منابع مشابه
Loss of Tankyrase-Mediated Destruction of 3BP2 Is the Underlying Pathogenic Mechanism of Cherubism
Cherubism is an autosomal-dominant syndrome characterized by inflammatory destructive bony lesions resulting in symmetrical deformities of the facial bones. Cherubism is caused by mutations in Sh3bp2, the gene that encodes the adaptor protein 3BP2. Most identified mutations in 3BP2 lie within the peptide sequence RSPPDG. A mouse model of cherubism develops hyperactive bone-remodeling osteoclast...
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We describe a novel missense mutation (Aspartic acid to Asparagine, p.D419N (g.1371G>A, c.1255G>A) within exon 9 of SH3BP2 in a patient with cherubism, an autosomal dominant syndrome characterized by excessive osteoclastic bone resorption of the jaw. Two siblings and the father were carriers but lacked phenotypic features. Transient expression of p.D419N (c.1255G>A), as well as three previously...
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Mutations in the SH3-domain binding protein 2 (SH3BP2) are known to cause a rare childhood disorder called cherubism that is characterized by inflammation and bone loss in the jaw, but the mechanism has remained unclear. In this issue, Ueki et al. (Ueki et al., 2007) now demonstrate that a cherubism mutation activates mouse Sh3bp2 resulting in enhanced production of the cytokine TNF-alpha by my...
متن کاملThe role of SH3BP2 in the pathophysiology of cherubism
Cherubism is a rare bone dysplasia that is characterized by symmetrical bone resorption limited to the jaws. Bone lesions are filled with soft fibrous giant cell-rich tissue that can expand and cause severe facial deformity. The disorder typically begins in children at ages of 2-5 years and the bone resorption and facial swelling continues until puberty; in most cases the lesions regress sponta...
متن کاملVariable expressivity familial cherubism: woman transmitting cherubism without suffering the disease
UNLABELLED Cherubism is classified within the group of benign osteo-fibrous lesions. Aside from facial deformities, it may account for major complications. It has been observed that the disease is caused by a mutation in the gene SH3BP2 (SH3-domain binding protein 2), which is located at chromosome 4pl6.3. Here we present two cases of familial cherubism, uncle and nephew, with variable clinical...
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ورودعنوان ژورنال:
- Cell
دوره 147 شماره
صفحات -
تاریخ انتشار 2011