Lee EJ, Cho M, Rho SB, Park J, Chae DA, Nguyen QTT

?-transducin repeats-containing protein-1 (?-TrCP1) serves as the substrate recognition subunit for SCF?-TrCP E3 ubiquitin ligases, which specifically ubiquitinate phosphorylated substrates. Three variants of ?-TrCP1 are known and act as homodimer or heterodimer complexes. Here, we identified a novel full-sequenced variant, ?-TrCP1-variant 4, which harbours exon II instead of exon III ...

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of variant 1, with no change in the open reading frame. The expression of ?-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, ?-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, ?-TrCP1-variant 4 directly interacts with ?-catenin, one of the substrates of SCF?-TrCP E3 ubiquitin ligase and down-regulates the transcriptional activity and protein expression of ?-catenin with a significantly weaker effect than that by variants 1 and 2. However, the co-expression of ?-TrCP1-variant 4 with variant 1 in same proportion has no effect, whereas other combinations effectively down-regulate the activity of ?-catenin, indicating that the heterodimer of variants 1 and 4 has no function. Thus, ?-TrCP1-variant 4 could play a critical role in SCF?-TrCP E3 ligase-mediated ubiquitination by acting as a negative regulator of ?-TrCP1-variant 1.

Date: Jan. 19, 2021

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