title: Smad1 stabilization and delocalization in response to the blockade of BMP activity.
abstract: Signaling at the plasma membrane receptors is generally terminated by some form of feedback regulation, such as endocytosis and/or degradation of the receptors. BMP-Smad1 signaling can also be attenuated by BMP-induced expression of the inhibitory Smads, which are negative regulators of Smad1 transactivation activity and/or BMP antagonists. Here, we report on a novel Smad1 regulation mechanism that occurs in response to the blockade of BMP activity. Lowering the serum levels or antagonizing BMPs with noggin led to upregulation of Smad1 at the protein level in several cell lines, but not to upregulation of Smad5, Smad8 or Smad2/3. The Smad1 upregulation occurs at the level of protein stabilization. Upregulated Smad1 was relocalized to the perinuclear region. These alterations seem to affect the dynamics and amplitude of BMP2-induced Smad1 reactivation. Our findings indicate that depleting or antagonizing BMPs leads to Smad1 stabilization and relocalization, thus revealing an unexpected regulatory mechanism for BMP-Smad1 signaling.
authors.affiliation: Department of Histology and Embryology, Shandong University School of Medicine 44#, Wenhua Xi Road, Jinan, Shandong, 250012, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Li
authors.forename: Jianhe
authors.initials: J
authors.lastname: Wang
authors.forename: Jenny Fung Ling
authors.initials: JF
authors.lastname: Chau
authors.forename: Huijuan
authors.initials: H
authors.lastname: Liu
authors.forename: Baojie
authors.initials: B
authors.lastname: Li
authors.forename: Aijun
authors.initials: A
authors.lastname: Hao
authors.forename: Jing
authors.initials: J
authors.lastname: Li
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D015153:Blotting, Western; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019556:COS Cells; D002352:Carrier Proteins / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media / Q000378:metabolism / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000166:cytology; D053595:Embryonic Stem Cells / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D044967:Serum / Q000378:metabolism; D051898:Smad1 Protein / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D000099176:Noggin Protein
chemical_list: D052005:Bone Morphogenetic Protein Receptors, Type I; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D003470:Culture Media; D016895:Culture Media, Serum-Free; D051898:Smad1 Protein; D000099176:Noggin Protein; C498212:Bmpr1a protein, mouse