β-TrCP1-variant 4, a novel splice variant of β-TrCP1, is a negative regulator of β-TrCP1-variant 1 in β-catenin degradation
Autor: | Dhan-Ah Chae, Eun-Ju Lee, Que Thanh Thanh Nguyen, Seung Bae Rho, Min-Ji Cho, Junsoo Park |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
biology Chemistry Protein subunit Alternative splicing Biophysics Cell Biology Biochemistry Ubiquitin ligase Cell biology 03 medical and health sciences Exon Open reading frame 030104 developmental biology 0302 clinical medicine Ubiquitin 030220 oncology & carcinogenesis Catenin biology.protein Phosphorylation Molecular Biology |
Zdroj: | Biochemical and biophysical research communications. 542 |
ISSN: | 1090-2104 |
Popis: | β-transducin repeats-containing protein-1 (β-TrCP1) serves as the substrate recognition subunit for SCFβ-TrCP E3 ubiquitin ligases, which specifically ubiquitinate phosphorylated substrates. Three variants of β-TrCP1 are known and act as homodimer or heterodimer complexes. Here, we identified a novel full-sequenced variant, β-TrCP1-variant 4, which harbours exon II instead of exon III of variant 1, with no change in the open reading frame. The expression of β-TrCP1-variant 4 is lower than that of variant 1 or 2 in ovarian cancer cell lines, whereas it is abundantly expressed in normal and cancerous ovarian tissues. Moreover, β-TrCP1-variant 2 was aberrantly expressed more than variant 1 in ovarian cancer tissues whereas variant 1 was expressed more in normal tissues. Similar to variants 1 and 2, β-TrCP1-variant 4 directly interacts with β-catenin, one of the substrates of SCFβ-TrCP E3 ubiquitin ligase and down-regulates the transcriptional activity and protein expression of β-catenin with a significantly weaker effect than that by variants 1 and 2. However, the co-expression of β-TrCP1-variant 4 with variant 1 in same proportion has no effect, whereas other combinations effectively down-regulate the activity of β-catenin, indicating that the heterodimer of variants 1 and 4 has no function. Thus, β-TrCP1-variant 4 could play a critical role in SCFβ-TrCP E3 ligase-mediated ubiquitination by acting as a negative regulator of β-TrCP1-variant 1. |
Databáze: | OpenAIRE |
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