The Nuclear Protein UHRF2 Is a Direct Target of the Transcription Factor E2F1 in the Induction of Apoptosis

Abstract

Background: E2F1-induced apoptosis kills oncogene-stressed cells, and regulators of this process may act as tumor suppressors. Results: We identified UHRF2 in a functional screen for mediators of E2F1 induced apoptosis. Conclusion: UHRF2 binds directly to E2F1 and is required for E2F1 induction of apoptosis and expression of several important apoptosis inducers. Significance: UHRF2 is a suspected tumor suppressor and our work suggests an anti-tumor mechanism.

Identification of UHRF2 as a Negative Regulator of Epithelial-Mesenchymal Transition and Its Clinical Significance in Esophageal Squamous Cell Carcinoma

“…Additionally, low expression of UHRF2 was found to be associated with vascular invasion, the malignant phenotype related to EMT, and poorer outcome regardless of tumor location or UICC stage. These inconsistent findings suggest that UHRF2 may be involved in organ-specific mechanisms through its multiple domains [16-20]. Thus, additional studies are needed to further elucidate the complex mechanisms of UHRF2 function.…”

“…The multiple domains of UHRF2 lead to complex functions; indeed, UHRF2 has been shown to be involved in the cell cycle network, epigenetic system, and ubiquitin proteasome system [13-15]. Hence, in several cancers, UHRF2 is dysregulated and acts as an oncogene [16, 17] or tumor-suppressor gene [18-20]. However, little is known about the biological and clinicopathological significance of UHRF2 in ESCC.…”

The update on transcriptional regulation of autophagy in normal and pathologic cells: A novel therapeutic target

“…For another, E2F transcription factors can compete with NF-kappa B for binding at the Bnip3 (a positive regulator of autophagy) promoter, and attenuate the induction of Bnip3 by HIF-1 alpha [169]. Of note, AMPK alpha 2, an inducer of autophagy, is an E2F1 target gene required for its apoptotic activity, which would be interesting to elucidate the possible role AMPK alpha 2 has in E2F1-induced autophagy and to understand the relationship between E2F1-induced autophagy and E2F1-induced apoptosis [170][171][172]. 7.…”

CINSARC signature as a prognostic marker for clinical outcome in sarcomas and beyond

“…The role of E2F transcription factors in controlling the gene expression central to the cell cycle and cell fate decisions has been well documented, and there is evidence of a complex combinatorial mechanism of gene regulation involving E2F proteins together with other cooperating transcriptional regulators . This includes regulatory cascades in which E2Fs activate the expression of genes encoding other transcription factors and then cooperate with these induced factors to regulate additional target genes, a relationship known as a feed‐forward regulatory loop . This has been reported for E2F1 and NFYB as well as for DREAM and FOXM1, the latter belonging to the CINSARC gene set.…”