Contributions of E3 ubiquitin-protein ligase TRIM33 to CXXC5-mediated gene expressions

Date

2024-8-27

Author

Ayten, Hazal

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17β-estradiol (E2), the main circulating estrogen hormone, plays important roles in regulating many physiological and pathophysiological events in varying tissues including the breast tissue where it acts as a mitogenic factor. E2 exerts its effects in the breast tissue by binding to the transcription factor estrogen receptors α and β (ERs) which regulates the expression of genes important for cellular proliferation, motility, and death. Our previous studies showed that the E2-ERα signaling regulates CXXC5 expression. CXXC5 acts as an epigenetic and transcription factor by binding to DNA. Although CXXC5 contributes to cellular proliferation and differentiation, its action mechanisms are unclear. Aimed at understanding CXXC5 action, our ongoing studies suggest that cell cycle-dependent synthesis of CXXC5 participates in the transition of MCF7 cells derived from a breast adenocarcinoma to the S phase in the cell cycle. We find that CXXC5 is ubiquitinated but its degradation through the ubiquitin-proteasome pathway is independent of cell cycle phases. To assess the underlying features of CXXC5 ubiquitination, my thesis studies initially explored the roles of E3 ubiquitin-protein ligases TRIM25 and TRIM33, both of which we had previously identified using BioID-MS as possible interactors of CXXC5, on the ubiquitination of CXXC5. I verified that only TRIM33 interacts with the DNA binding CXXC domain of CXXC5. However, TRIM33 does not appear to affect the ubiquitination or degradation of CXXC5 but contributes to CXXC5-mediated gene expressions. These findings suggest that TRIM33 acts as a transcriptional co-regulator for CXXC5.

Subject Keywords

Estrogen Signaling, CXXC5, TRIM33, Ubiquitination, Gene Regulation

URI

https://hdl.handle.net/11511/110995

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Graduate School of Natural and Applied Sciences, Thesis