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

被引:70
作者
Raju, GP
Dimova, N
Klein, PS
Huang, HC [1 ]
机构
[1] Univ Penn, Med Ctr, Dept Med, Philadelphia, PA 19104 USA
[2] Univ Penn, Med Ctr, Cell & Mol Biol Grad Grp, Philadelphia, PA 19104 USA
[3] Univ Penn, Med Ctr, Howard Hughes Med Inst, Philadelphia, PA 19104 USA
关键词
D O I
10.1074/jbc.M210505200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 BW/Smad1 signaling.
引用
收藏
页码:428 / 437
页数:10
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