tailieunhanh - Báo cáo khoa học: What MAN1 does to the Smads TGFb/BMP signaling and the nuclear envelope Luiza Bengtsson

The inner nuclear membrane protein MAN1 has been identified as an important factor in transforming growth factor b⁄bone morphogenic pro-tein (TGFb⁄BMP) signaling. Loss of MAN1 results in three autosomal dominant diseases in humans; all three characterized by increased bone density. | MINIREVIEW What MAN1 does to the Smads TGFp BMP signaling and the nuclear envelope Luiza Bengtsson Institute for Chemistry and Biochemistry Free University Berlin Germany Keywords BMP laminopathy MAN1 nuclear envelope phosphatase signal transduction Smad TGFp Correspondence L. Bengtsson Institute for Chemistry and Biochemistry Free University Berlin Thielallee 63 14195 Berlin Germany Tel 49 30 838 54789 E-mail lbengts@ Previous address Department of Cell Biology Johns Hopkins University Schoolof Medicine 725 N. Wolfe St Baltimore MD 21205 USA Received 8 March 2006 accepted 8 January 2007 doi The inner nuclear membrane protein MAN1 has been identified as an important factor in transforming growth factor p bone morphogenic protein TGFp 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 TGFp BMP signaling. Several independent studies have shown that MAN1 is antagonizing TGFp BMP signaling through binding to regulatory Smads. Here recent progress in understanding MAN1 functions is summarized and a model for MAN1-dependent regulation of TGFp BMP signaling is proposed. Introduction Our knowledge about the nuclear membrane has advanced dramatically in the recent years. We now know that protein residents of the nuclear membrane regulate processes as diverse as DNA replication and transcription control of the shape and stability of the nucleus cell cycle progression chromatin organization cell development and differentiation nuclear anchoring and migration and apoptosis reviewed in 1 2 . Mutations in several of the integral membrane proteins of the inner nuclear membrane emerin MAN1 lamin B receptor and their common binding partners lamins cause distinct diseases the molecular mechanisms of which

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