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• W3128547306 endingPage "242" @default.
• W3128547306 startingPage "225" @default.
• W3128547306 abstract "Cancer resistance to current therapeutics in a large subset of patients is a major problem that is challenging and deserves immediate resolution. One such factor is the overexpressed transcription factor Yin Yang 1 (YY1) that has been reported to regulate cancer cell resistance to irradiation, chemotherapeutics and immunotherapeutics. Hence, delineating the biochemical, molecular, and genetics mechanisms underlying YY1 regulation to resistance may provide new therapeutic targets and new prognostic/diagnostic biomarkers. One mechanism by which YY1 regulates resistance is through the inhibition of the tumor suppressor phosphatase and tensin homolog (PTEN) and, thus, activation of the PI3K/AKT and NF-KB survival/antiapoptotic pathways, thereby significantly regulating resistance. More recently a new mechanism of YY1-mediated resistance has been reported and consists of YY1-induced inhibition of DNA damage repair. This is accomplished by the role of YY1 and ADP-ribosylation and YY1 suppression of the Flap endonuclease 1 (FEN1). In addition, YY1 mediates the translocation of phosphorylated PTEN (pPTEN). This is accomplished by drug-induced stress that upregulates the expressions of YY1 and pPTEN. The overexpression of YY1 inhibits the PP2A phosphatase activity that, in turn, fails to dephosphorylate PTEN and promotes translocation to the nucleus. In the nucleus, pPTEN forms a complex with Ki67 and with both H2AX and Rad51 (DNA repair enzymes), resulting in the induction of DNA repair and resistance to the drugs. Downregulation of YY1 reverses resistance, and the cancer cells become sensitive to drug-induced cytotoxicity and cell death. Of note the phosphorylation of PTEN and its translocation was reported at the phosphorylation of different amino acid residues by various authors and may be attributed to different cancers examined. These findings establish the novel YY1/PTEN/PP2A/H2AX/Rad51 axis in the regulation of resistance. This axis provides a new approach to target gene products in this axis for new therapeutics and new prognostic/diagnostic biomarkers." @default.
• W3128547306 created "2021-02-15" @default.
• W3128547306 creator A5055490703 @default.
• W3128547306 date "2021-01-01" @default.
• W3128547306 modified "2023-09-26" @default.
• W3128547306 title "The role of YY1 in drug resistant cancer: Involvement of the YY1/PTEN/PP2A/H2Ax/Rad51 axis" @default.
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