Cyclin E-CDK2 Protein Phosphorylates Plant Homeodomain Finger Protein 8 (PHF8) and Regulates Its Function in the Cell Cycle

Abstract

Background: Cyclin E-CDK2 is a key protein kinase in the cell cycle. Results: Phosphorylation of PHF8 by cyclin E-CDK2 enhances its demethylase activity toward H3K9me2 and promotes rDNA transcription as well as S phase progression. Conclusion: Cyclin E-CDK2-dependent phosphorylation of PHF8 affects its function. Significance: We unveiled the mechanism of how cyclin E-CDK2 regulates the function of PHF8 in cell cycle regulation.

Histone demethylases in chromatin biology and beyond

“…This is exemplified by the demethylase KDM7B, which binds to the promoters of several key cell cycle regulators, including E2F1 target genes, and is required for their transcriptional activation by removing the repressive H3K9me1/2 and H4K20me1 . In keeping with this role, KDM7B protein levels and its binding to chromatin are highly regulated during the cell cycle and this appears to play important roles in the G1/S and G2/M transitions . Similarly, KDM1A positively regulates the expression of MAD2 and BUBR1, which are part of the mitotic checkpoint complex and are required for proper chromosome segregation during mitosis .…”

“…Phosphorylation‐dependent activation of KDM7C stimulates its interaction with the DNA‐binding protein ARID5B, leading to the recruitment of the demethylase complex to chromatin, presumably through the generic DNA‐binding activity of ARID5B . Similarly, phosphorylation by Cyclin E‐CDK2 stimulates the H3K9me1/2 demethylase activity of the related protein KDM7B and this plays a role in the regulation of gene expression during cell cycle progression . In addition to these specific examples where post‐translational modifications control enzymatic activity, ubiquitylation and proteasomal degradation are emerging as key determinants in regulating the levels of histone demethylases.…”

“…Control of cell cycle timing and dynamics is essential for proper cell division and recent work has demonstrated that histone demethylases play several distinct roles in controlling normal cell division (Fig ) . One specific way this is achieved is through their capacity to directly regulate the expression of genes required for normal cell cycle progression . This is exemplified by the demethylase KDM7B, which binds to the promoters of several key cell cycle regulators, including E2F1 target genes, and is required for their transcriptional activation by removing the repressive H3K9me1/2 and H4K20me1 .…”

Dehydration‐responsive nuclear proteome landscape of chickpea (Cicer arietinum L.) reveals phosphorylation‐mediated regulation of stress response

“…Interplay between kinases and phosphatases mediates global regulation of cellular function (Li et al, ; Trotta, Konert, Rahikainen, Aro, & Kangasjärvi, ; Zhao et al, ). The reversibility of protein phosphorylation status further aids in plasticity of molecular regulation spreading its influence over replication, transcription, cell cycle progression, splicing, and epigenetic regulation (Hur et al, ; Qi et al, ; Sun et al, ; Tunc‐Ozdemir et al, ). The precise site of phosphorylation has been the study of interest in deciphering signal transduction pathways (Nühse, Stensballe, Jensen, & Peck, ).…”

Low and High Molecular Weight FGF-2 Have Differential Effects on Astrocyte Proliferation, but Are Both Protective Against Aβ-Induced Cytotoxicity

“…Cyclin D1 functions as a regulatory subunit of CDK4 or CDK6, and the activity is required for the cell cycle progression through G1 phase (Chen et al, 2018). Cyclin E forms a complex with CDK2 and plays a critical role in the transition from G1 to S phase, thus regulating proliferation (Sun et al, 2015). c-Myc regulates gene expression through the binding on the Enhancer Box sequence (E-boxes) and recruiting histone acetyltransferases (Xiong et al, 2010).…”