What MAN1 does to the Smads. TGFbeta/BMP signaling and the nuclear envelope.
The inner nuclear membrane protein MAN1 has been identified as an important factor in transforming growth factor beta/bone morphogenic protein (TGFbeta/BMP) signaling. Loss of MAN1 results in three autosomal dominant diseases in humans; all three characterized by increased bone density. Xenopus embryos lacking MAN1 develop severe morphological defects. Both in humans and in Xenopus embryos the defects originate from deregulation of TGFbeta/BMP signaling. Several independent studies have shown that MAN1 is antagonizing TGFbeta/BMP signaling through binding to regulatory Smads. Here, recent progress in understanding MAN1 functions is summarized and a model for MAN1-dependent regulation of TGFbeta/BMP signaling is proposed.
Bengtsson
Luiza
L
Institute for Chemistry and Biochemistry, Free University Berlin, Thielallee 63, 14195 Berlin, Germany. lbengts@chemie.fu-berlin.de
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D009685:Nuclear Envelope / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; C405329:LEMD3 protein, human; D008565:Membrane Proteins; D009687:Nuclear Proteins; D051785:Smad Proteins; D016212:Transforming Growth Factor beta