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Smad1 stabilization and delocalization in response to the blockade of BMP activity

Cellular & Molecular Biology Letters volume 18, pages 340–354 (2013)Cite this article

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.

Abbreviations

BMP:

bone morphogenetic proteins

BMPRII:

BMP receptor II

MEFs:

mouse embryonic fibroblasts

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Authors and Affiliations

  1. Department of Histology and Embryology, Shandong University School of Medicine, 44#, Wenhua Xi Road, Jinan, Shandong, 250012, China

    Lili Li & Aijun Hao

  2. Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China

    Lili Li, Huijuan Liu & Baojie Li

  3. Institute of Molecular and Cell Biology, Singapore, Singapore

    Jianhe Wang & Jenny Fung Ling Chau

  4. Department of Ophthalmology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Jing Li

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  1. Lili Li
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  2. Jianhe Wang
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Correspondence to Jing Li.

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Li, L., Wang, J., Chau, J.F.L. et al. Smad1 stabilization and delocalization in response to the blockade of BMP activity. Cell Mol Biol Lett 18, 340–354 (2013). https://doi.org/10.2478/s11658-013-0093-0

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  • DOI: https://doi.org/10.2478/s11658-013-0093-0

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Cellular & Molecular Biology Letters

ISSN: 1689-1392

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