Interaction of the epigenetic integrator UHRF1 with the MYST domain of TIP60 inside the cell

Ashraf, Waseem; Bronner, Christian; Zaayter, Liliyana; Ahmad, Tanveer; Richert, Ludovic; Alhosin, Mahmoud; Ibrahim, Alì; Hamiche, Ali; Mousli, Marc

doi:10.1186/s13046-017-0659-1

Cited by 22 publications

(26 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have previously shown that TIP60 overexpression downregulates UHRF1 and DNMT1 [57]. Here, we con rm by confocal microscopy experiments that a signi cant decrease in UHRF1 and DNMT1 uorescence intensity was detected in TIP60-eGFP WT transfected cells while TIP60ΔMYST-eGFP transfection only marginally affected UHRF1 and DNMT1 uorescence intensity ( Figure S1).…”

Section: Tip60 Overexpression Induces Ubiquitination Of Uhrf1supporting

confidence: 78%

“…TIP60 is thought to have a tumor suppressor role by maintaining the cellular and genomic stability [25,41,45,51,52,53,54,55,56]. UHRF1 directly interacts with the MYST domain of TIP60 [57] and regulates TIP60 expression and activity [25,27]. There is thus a fragile balance between UHRF1 and TIP60 broken in favour of UHRF1 in cancers.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, targeting UHRF1 in cancer cells would permit to rescue p53 levels and enhance the coordinated dialogue between p53 and TIP60. In a previous study, we have shown that UHRF1 interacts with the MYST domain of TIP60 [57]. Moreover, UHRF1 through its E3 ligase activity, ubiquitinates DNMT1 and by this way impacts its levels [17,58,59].…”

Section: Introductionmentioning

confidence: 87%

“…Moreover, UHRF1 through its E3 ligase activity, ubiquitinates DNMT1 and by this way impacts its levels [17,58,59]. Although it has already been shown that TIP60 overexpression down regulates UHRF1 levels in HeLa cells [57], the mechanism of the TIP60-mediated UHRF1 down-regulation in cancer cells remains elusive. Here, we demonstrate that TIP60 interferes with the UHRF1-USP7 association.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

TIP60 governs the auto-ubiquitination of UHRF1 through USP7 dissociation from the UHRF1/USP7 complex

Ahmad

Ashraf

Ibrahim

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

Background: The epigenetic regulator UHRF1 (Ubiquitin-like, containing PHD and RING finger domains 1) plays an essential role in faithful transmission of DNA methylation during replication. It has tumorogenesis potential and is overexpressed in cancers. TIP60 (Tat interactive protein, 60 kDa) is an important partner of UHRF1, ensuring various cellular processes through its acetyltransferase activity. TIP60 is believed to exert a tumor suppressive role partly explained by its down-regulation in many cancers. Both proteins participate in various cellular functions such as chromatin remodeling, cell cycle, DNA damage repair and regulation of protein stability.Methods: Immunoprecipitation and confocal microscopy techniques were performed to study the ubiquitination of UHRF1 and USP-UHRF1 association. Fluorescence lifetime imaging microscopy (FLIM) technique was performed to analyze the interaction between UHRF1 and ubiquitin inside the nucleus. Western blotting was used to assess the effect of TIP60 overexpression on p73, pro- and anti-apoptotic proteins. TIP60-mediated apoptosis in HeLa cells was investigated by flow cytometry. Results were statistically analyzed using Graphpad prism.Results: Herein, our goal was to investigate the role and mechanism of TIP60 in the regulation of UHRF1 expression. Our results showed that TIP60 overexpression down-regulated UHRF1 and DNMT1 (DNA methyltransferase 1) expressions. TIP60 interfered with USP7-UHRF1 association and induced degradation of UHRF1 in an auto-ubiquitination dependent pathway. Moreover, TIP60 activated the p73-mediated apoptotic pathway.Conclusion: Taken together, our data suggest that the tumor suppressor role of TIP60 is mediated by its regulation to UHRF1.

show abstract

Section: Tip60 Overexpression Induces Ubiquitination Of Uhrf1supporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

TIP60 governs the auto-ubiquitination of UHRF1 through USP7 dissociation from the UHRF1/USP7 complex

Ahmad

Ashraf

Ibrahim

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…kat5, a histone acetyltransferase that induces USP7/DNMT1 destabilization and proteasomal degradation [106,107].…”

Section: Primers Design and Validationmentioning

confidence: 99%

The anti-lipidemic drug simvastatin modulates Epigenetic Biomarkers in the AmphipodGammarus locusta

Alves¹,

Neuparth²,

Barros³

et al. 2020

Preprint

View full text Add to dashboard Cite

The adverse effects of certain environmental chemicals have been recently associated with epigenome´s modulation. Although the changes in the epigenetic signature are still not integrated into hazard and risk assessment, they are interesting candidates for linking environmental exposures to altered phenotypes given that these changes may be passed across multiple non-exposed generations. Here, we addressed the effects of simvastatin (SIM), one of the most prescribed human pharmaceuticals, in epigenetic regulators of the amphipod Gammarus locusta, as a proxy to support its integration in hazard and environmental risk assessment. SIM is a known modulator of epigenome in mammalian cell lines, and has been reported to impact G. locusta ecological endpoints at environmentally relevant levels. G. locusta juveniles were exposed to three SIM concentrations (0.32, 1.6 and 8 µg.L -1 ), for 15 days. The basal expression of selected epigenetic regulators was determined, along with the quantification of DNA methylation levels and the assessment of key ecological endpoints. Exposure to 0.32 and 8 µg.L -1 SIM induced significant downregulation of DNA methyltransferase1 (dnmt1), concomitantly with Global DNA hypomethylation and impact on growth. Overall, this work is the first to validate the basal expression of key epigenetic regulators in a keystone marine crustacean, supporting the integration of epigenetic biomarkers into hazard assessment frameworks.

show abstract

Protein acetylation: a novel modus of obesity regulation

et al. 2021

View full text Add to dashboard Cite

Interaction of the epigenetic integrator UHRF1 with the MYST domain of TIP60 inside the cell

Cited by 22 publications

References 66 publications

TIP60 governs the auto-ubiquitination of UHRF1 through USP7 dissociation from the UHRF1/USP7 complex

TIP60 governs the auto-ubiquitination of UHRF1 through USP7 dissociation from the UHRF1/USP7 complex

The anti-lipidemic drug simvastatin modulates Epigenetic Biomarkers in the AmphipodGammarus locusta

Protein acetylation: a novel modus of obesity regulation

Contact Info

Product

Resources

About