The C/EBP proteins form a family of transcription factors with at least seven members. These proteins consist of three structural components which include a C-terminal leucine-zipper, a basic DNA-binding region and a N-terminal transactivating region. Dimerization through the leucine-zipper leads to formation of homo- and heterodimers which then bind with their two basic regions to often non-symmetric DNA-sequences in the promoter/enhancer regions of a variety of genes. Expression of C/EBP is prominent in adipocytes, hepatocytes and monocytes/macrophages, and here these proteins are involved in tissue-specific gene expression. Target genes for C/EBP include those for acute phase response genes in liver cells and for cytokine genes in monocytes/macrophages[3]. C/EBP alpha is concentrated in the upper epidermis in a predominantly cytoplasmic location within cells, whereas the highest levels of C/EBP beta and CHOP are seen in the mid-epidermis, mainly within nuclei. High levels of C/EBP beta and CHOP (but not C/EBP alpha) are also observed in hair follicles and sebaceous glands[4]. C/EBPalpha is a particularly potent regulator of cell-cycle exit and is induced in terminally differentiating adipocytes and myeloid cells, where it also activates differentiation-specific genes. The growth-inhibiting activity of C/EBPalpha suppresses tumorigenesis in myeloid cells and possibly other tissues[5]. ICCB280 was capable of inducing differentiation and apoptosis of ATRA-resistant patient blasts strongly signify that the activity of this compound can overcome resistance to other current therapies for AML with an unfavorable prognosis. ICCB280 (10 μM; 2-8 d) increases the C/EBPα expression (mRNA and protein) and modulates its target genes in HL-60 cells. ICCB280 (0.1-50 μM; 48 h) suppresses the HL-60 cell growth, with an IC50 of 8.6 μM[1].
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