AIMP1/p43 downregulates TGF-{beta} signaling via stabilization of smurf2
- Division of Life Sciences, Graduate School of Biotechnology, Korea University, Seoul 136-701 (Korea, Republic of)
- Center for Medicinal Protein Network and Systems Biology, College of Pharmacy, Seoul National University, Seoul 151-74 2 (Korea, Republic of)
- Department of Biochemistry, College of Medicine, Institute of Medical Research, Chungbuk National University, Cheongju 361-763 (Korea, Republic of)
AIMP1 (also known as p43) is a factor associated with a macromolecular aminoacyl-tRNA synthetase (ARS) complex but also plays diverse regulatory roles in various physiological processes. Here, we report that AIMP1 negatively regulates TGF-{beta} signaling via stabilization of Smurf2. TGF-{beta}-dependent phosphorylation and nuclear localization of R-Smads, induction of target genes, and growth arrest were increased in AIMP1-deficient or -suppressed cells. In AIMP1-deficient or suppressed cells, the Smurf2 level was decreased. Various binding assays demonstrated the direction interaction of the C-terminal region of AIMP1 directly with the Smad7-binding region of Smurf2. The association of Smurf2 with Smad7 and its ubiquitination were inhibited by AIMP1, thereby protecting its autocatalytic degradation stimulated by Smad7. Thus, this work suggests the novel activity of AIMP1 as a component of negative feedback loop of TGF-{beta} signaling.
- OSTI ID:
- 21143738
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 371, Issue 3; Other Information: DOI: 10.1016/j.bbrc.2008.04.099; PII: S0006-291X(08)00748-1; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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