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

Cellular & Molecular Biology Letters

Huijuan Liu¹  Jing Li⁴  Aijun Hao²  Baojie Li¹  Jenny Fung Ling Chau⁵  Lili Li³  Jianhe Wang⁵ 

[1] Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China$$;Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong, China$$;Department of Histology and Embryology, Shandong University School of Medicine, Jinan, Shandong, China$$Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China$$;Department of Ophthalmology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China$$;Institute of Molecular and Cell Biology, Singapore, Singapore$$

关键词: Smad1;    BMPs;    Feedback regulation;    Degradation;    Noggin;    BMPRIA;    PPM1A;    Serum starvation;    Intestinal villi;    Smad2/3;   

DOI  :  10.2478/s11658-013-0093-0

学科分类：分子生物学，细胞生物学和基因

来源: Uniwersytet Wroclawski * Wydzial Biotechnologii / University of Wroclaw, Faculty of Biotechnology

【 摘 要 】

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.

【 授权许可】

Unknown