期刊
JOURNAL OF ANTIBIOTICS
卷 64, 期 9, 页码 635-644出版社
JAPAN ANTIBIOTICS RESEARCH ASSOC
DOI: 10.1038/ja.2011.60
关键词
cancer therapy; Hsp90 inhibitor; signal-transduction pathway
Heat-shock protein 90 (Hsp90) inhibitor downregulates c-Myc expression and upregulates the expression of tumor repressor proteins such as p53 and pRB, inhibiting the G1/S transition and causing G2/M arrest during cell cycle progression. The cycle progression is extensively controlled by the pRB/E2F signaling pathway. E2F is released from the pRB/E2F complex with the phosphorylation of pRB by cyclin-cyclin-dependent kinase (CDK) complexes. The released E2F promotes the transcription of target genes involved in cell cycle progression. The pRB/E2F signaling pathway is controlled by DNA methyltransferase-1 (Dnmt-1). The elevated expression of Dnmt-1 has been reported in carcinomas of the colon, lung and prostate. A defect of pRB expression in Rb-/- cancer cells is caused by the aberrant methylation of CpG in the Rb promoter. The Hsp90 inhibitor disrupts the Dnmt-1/Hsp90 association and upregulates pRB expression. In this review, the Hsp90 inhibitors that show promise for cancer therapy are summarized. The Journal of Antibiotics (2011) 64, 635-644; doi: 10.1038/ja.2011.60; published online 3 August 2011
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