TRIM28 regulates transcriptional activity of methyl-DNA binding protein Kaiso by SUMOylation

• Published in: Biochimie 2023-03, Vol.206, p.73-80
• Main Authors: Lobanova, Y., Filonova, G., Kaplun, D., Zhigalova, N., Prokhortchouk, E., Zhenilo, S.
• Format: Article
• Language: English
• Subjects: DNA-Binding Proteins - genetics; Gene Expression Regulation; Kaiso; Methyl-dependent repression; Protein Binding; SUMO; Sumoylation; Transcription Factors - metabolism; TRIM28; Zinc Fingers
• ISSN: 0300-9084; 1638-6183
• DOI: 10.1016/j.biochi.2022.10.006

Kaiso is a methyl DNA binding transcriptional factor involved in cell cycle control, WNT signaling, colon inflammation, and cancer progression. Recently, it was shown that SUMOylation dynamically modulates the transcriptional activity of Kaiso. However, factors involved in SUMOylation of Kaiso are unknown. Here we show that TRIM28 enhances SUMOylation of Kaiso leading to a decreased methyl-dependent repression ability. TRIM28 is a scaffold protein that regulates transcription and posttranslational modifications of factors involved in cell cycle progression, DNA damage, and viral gene expression. It has SUMO and ubiquitin E3 ligase activity. Here, we defined the domains involved in Kaiso-TRIM28 interaction. The RBCC domain of TRIM28 interacts with the BTB/POZ domain and the zinc fingers of Kaiso. The PHD-bromodomain of TRIM28 is sufficient for the interaction with zinc fingers of Kaiso. Additionally, we found that Kaiso enhances SUMOylation of TRIM28. Altogether our data suggest self-enhancement of SUMOylation of both Kaiso and TRIM28 that affects transcriptional activity of Kaiso. •BTB/POZ domain of Kaiso interacts with RBCC domain of TRIM28.•Zinc fingers of Kaiso interact with RBCC and PHD-bromodomain of TRIM28.•TRIM28 enhances a SUMOylation level of Kaiso and vice versa.•TRIM28 decreases the repressive effect of Kaiso.