Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
J Biol Chem. January 3, 2003; 278 (1): 428-37.

SANE, a novel LEM domain protein, regulates bone morphogenetic protein signaling through interaction with Smad1.

Raju GP , Dimova N , Klein PS , Huang HC .

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta (TGF-beta) superfamily that play important roles in bone formation, embryonic patterning, and epidermal-neural cell fate decisions. BMPs signal through pathway specific mediators such as Smads1 and 5, but the upstream regulation of BMP-specific Smads has not been fully characterized. Here we report the identification of SANE (Smad1 Antagonistic Effector), a novel protein with significant sequence similarity to nuclear envelop proteins such as MAN1. SANE binds to Smad1/5 and to BMP type I receptors and regulates BMP signaling. SANE specifically blocks BMP-dependent signaling in Xenopus embryos and in a mammalian model of bone formation but does not inhibit the TGF-beta/Smad2 pathway. Inhibition of BMP signaling by SANE requires interaction between SANE and Smad1, because a SANE mutant that does not bind Smad1 does not inhibit BMP signaling. Furthermore, inhibition appears to be mediated by inhibition of BMP-induced Smad1 phosphorylation, blocking ligand-dependent nuclear translocation of Smad1. These studies define a new mode of regulation for intracellular BMP/Smad1 signaling.

PubMed ID: 12393873
Article link: J Biol Chem.
Grant support: AR45587 NIAMS NIH HHS

Genes referenced: lemd3 smad1 smad2 tgfb1

Xenbase: The Xenopus laevis and X. tropicalis resource.
Version: 4.8.2
Major funding for Xenbase is provided by the National Institute of Child Health and Human Development, grant P41 HD064556