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The E3 Ubiquitin Ligase TRIM21 Regulates Basal Levels of PDGFRβ.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2023 Apr 24; Vol. 24 (9). Date of Electronic Publication: 2023 Apr 24. - Publication Year :
- 2023
-
Abstract
- Activation of platelet-derived growth factor (PDGF) receptors α and β (PDGFRα and PDGFRβ) at the cell surface by binding of PDGF isoforms leads to internalization of receptors, which affects the amplitude and kinetics of signaling. Ubiquitination of PDGF receptors in response to ligand stimulation is mediated by the Casitas b-lineage lymphoma (Cbl) family of ubiquitin ligases, promoting internalization and serving as a sorting signal for vesicular trafficking of receptors. We report here that another E3 ligase, i.e., tripartite motif-containing protein 21 (TRIM21), contributes to the ubiquitination of PDGFRβ in human primary fibroblasts AG1523 and the osteosarcoma cell line U2OS and regulates basal levels of PDGFRβ. We found that siRNA-mediated depletion of TRIM21 led to decreased ubiquitination of PDGFRβ in response to PDGF-BB stimulation, while internalization from the cell surface and the rate of ligand-induced degradation of the receptor were not affected. Moreover, induction of TRIM21 decreased the levels of PDGFRβ in serum-starved cells, and even more in growing cells, in the absence of PDGF stimulation. Consistently, siRNA knockdown of TRIM21 caused accumulation of the total amount of PDGFRβ, both in the cytoplasm and on the cell surface, without affecting mRNA levels of the receptor. We conclude that TRIM21 acts post-translationally and maintains basal levels of PDGFRβ, thus suggesting that ubiquitination of PDGFRβ by TRIM21 may direct a portion of receptor for degradation in growing cells in a ligand-independent manner.
- Subjects :
- Humans
Carrier Proteins metabolism
Ligands
Phosphorylation physiology
Receptor, Platelet-Derived Growth Factor beta genetics
Receptor, Platelet-Derived Growth Factor beta metabolism
RNA, Small Interfering genetics
RNA, Small Interfering metabolism
Platelet-Derived Growth Factor metabolism
Ubiquitin-Protein Ligases genetics
Ubiquitin-Protein Ligases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 24
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 37175489
- Full Text :
- https://doi.org/10.3390/ijms24097782