Chk1 (Phospho-Ser301) ELISA Kit

Recent data support the notion that a group of key transcriptional regulators involved in tumorigenesis, including MYC, p53, E2F1, and BMI1, share an intriguing capacity to simultaneously regulate metabolism and cell cycle. Here, we show that another factor, the multifunctional protein E4F1, directly controls genes involved in mitochondria functions and cell-cycle checkpoints, including Chek1, a major component of the DNA damage response. Coordination of these cellular functions by E4F1 appears essential for the survival of p53-deficient transformed cells. Acute inactivation of E4F1 in these cells results in CHK1-dependent checkpoint deficiency and multiple mitochondrial dysfunctions that lead to increased ROS production, energy stress, and inhibition of de novo pyrimidine synthesis. This deadly cocktail leads to the accumulation of uncompensated oxidative damage to proteins and extensive DNA damage, ending in cell death. This supports the rationale of therapeutic strategies simultaneously targeting mitochondria and CHK1 for selective killing of p53-deficient cancer cells.

Aims and background: The objective of this study was to identify possible biomarkers and to explore the mechanisms of suppression of vemurafenib on melanoma progression. Methods: GSE42872 affymetrix microarray data were downloaded from the Gene Expression Omnibus database for further analysis. Differentially expressed genes (DEGs) between vehicle-treated samples and vemurafenib-treated samples were identified. Gene ontology and pathway enrichment analysis of DEGs were performed, followed by protein-protein interaction (PPI) network construction. Furthermore, the functional modules of the PPI network were screened using BioNet analysis tool. Finally, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed for DEGs in the module. Results: In total, 794 upregulated transcripts corresponding to 214 genes and 977 downregulated transcripts corresponding to 325 genes were screened. The downregulated DEGs were significantly enriched in pathways such as cell cycle, DNA replication, and p53 signaling pathway. Upregulated DEGs were significantly enriched in phosphatidylinositol signaling system and inositol phosphate metabolism. Significantly enriched functions of downregulated DEGs were mitotic cell cycle, nuclear division, DNA metabolic process, cell cycle, and mitosis. Upregulated DEGs were mainly enriched in single multicellular organism process and multicellular organismal process. Moreover, cell division cycle 6, checkpoint kinase 1 (CHEK1), E2F transcription factor 1 (E2F1), epidermal growth factor receptor (EGFR), and phosphoinositide-3-kinase, regulatory subunit 1-alpha (PIK3R1) of the module were remarkably enriched in pathways such as cell cycle, apoptosis, focal adhesion, and DNA replication. Conclusions: Cell division cycle 6, CHEK1, E2F1, EGFR, and PIK3R1 of the module and their relative pathways, cell cycle, and focal adhesion might play important roles of suppression of vemurafenib on melanoma progression.