oxaliplatin significantly increases the number of apoptotic cells. This observation was more buy ZM241385 dramatic in cells with defective Pokemon as compared to control cells. The function of silencing Pokemon in promoting apoptosis was further confirmed by FACS analysis. Based upon these findings, we investigated the molecular mechanism for Pokemon-mediated GSK137647A enhanced HCC apoptosis using the Apoptosis Antibody Array. Our data revealed upregulation of proteins involved in intrinsic and extrinsic apoptotic signaling pathways such as Bax, cytochrome c, Fas, FADD, caspase-3, HIF-1a and p53. The p53 tumor suppressor protein is one of the most studied proteins because of its status as ����guardian of the genome����. It constitutes the central node in a network of molecular interactions regulating the cellular response to stresses such as DNA damage and oncogene activation. Avery-Kieida et al reported that some p53 target genes involved in apoptosis and cell cycle arrest are aberrantly expressed in melanoma cells, leading to abnormal p53 activity and contributing to the proliferation and apoptosis of these cells. We found increased expression of checkpoint-related genes including ATM, BRCA1, BRCA2, CDKN1A, CHEK1, CUL1, CDKN2A and CDKN2B in HepG2 si-Pokemon cells. Altogether, this expression pattern resulted in cell cycle arrest at S phase. High p53 expression induces apoptosis in fetal liver erythroblasts, and erythroid-specific inactivation of the mouse Mdm2 gene, a key negative regulator of p53, leads to increased apoptosis in erythroblasts and embryonic lethality due to a severe anemia. p53 is also able to promote apoptosis through transcription-independent apoptotic mechanisms. Choi et al found that Pokemon acts as a master control of cellular transformation and proliferation by potently blocking the p53 pathway in HeLa cells. Our findings suggest that p53 expression and phosphorylation were significantly increased after treatment of oxaliplatin. These data suggest that Pokemon silencing enhancing apoptosis of HCC cells via the p53 pathway. p53 is involved in apoptotic induction through two apoptotic signaling pathways thought to be distinct until recently. The intrinsi
