What MAN1 does to the Smads. TGFbeta/BMP signaling and the nuclear envelope

FEBS J. 2007 Mar;274(6):1374-82. doi: 10.1111/j.1742-4658.2007.05696.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bone Morphogenetic Proteins / metabolism*
  • DNA-Binding Proteins
  • Humans
  • Membrane Proteins / metabolism*
  • Nuclear Envelope / metabolism*
  • Nuclear Proteins / metabolism*
  • Phosphorylation
  • Signal Transduction*
  • Smad Proteins / metabolism*
  • Transforming Growth Factor beta / metabolism*


  • Bone Morphogenetic Proteins
  • DNA-Binding Proteins
  • LEMD3 protein, human
  • Membrane Proteins
  • Nuclear Proteins
  • Smad Proteins
  • Transforming Growth Factor beta