Ell cycle regulation. Pon-A Exposure of SYK-deficient U373 cells stably transfected with wildtype SYK gene Salicyluric acid Autophagy induces expression of SYK and activates downstream signaling events mimicking oxidative stress-induced activation of SYK and SYK-dependent signal transduction pathways (Uckun et al., 2010a). To be able to acquire insights in to the function of SYK as a centrosomal protein, we initial examined the effect of SYK expression levels around the expression levels of cell cycle regulatory genes in human cells making use of this ecdysoneinducible mammalian expression technique (Uckun et al., 2010a). The eukaryotic cell division cycle has been shown to rely on an intricate sequence of transcriptional events associated with distinct cell cycle regulated gene expression patterns (Rowicka et al., 2007). Gene set enrichment analysis (GSEA) showed that SYK induction in U373 cells causes a significant down-regulation of evolutionarily conserved genes connected with mitosis (Fig. 2a, normalized enrichment score: -2.48, false discovery price b 0.0001, P b 0.0001) and cell cycle progression (Fig. 2b, normalized enrichment score: -2.44, false discovery price b 0.0001, P b 0.0001).The down-regulated genes in SYK-induced U373 cells integrated the human homologs of 5 yeast genes (viz.: CDC20, TAL1, PGM2, DBF4, BUB3) (Fig. 2c ) previously demonstrated to possess peak expression in the G2 and M phases of the yeast cell cycle. Data for the cell cycle specific expression of those yeast genes was determined by high-resolution timing of cell cycle-regulated gene expression determined by genome-wide gene expression information of synchronized yeast cultures (Rowicka et al., 2007). Among the 53 down-regulated genes, the most significantly affected 10 genes exhibiting the greatest fold-difference values were PTTG1 (10.4-fold decrease, P = 0.0097), Diflucortolone valerate In Vitro UBEC2C (eight.5-fold decrease, P = 0.0033), CDC20 (eight.4-fold lower, P = 0.002), AURKA (8.3-fold reduce, P = 0.0059), CDC25C (7.8-fold reduce ,GSE18798 P = 0.0076), CCNB1 (7.4-fold decrease, P = 0.0045), CCNB2 (six.8-fold decrease, P = 0.0029), BUB1B (six.4-fold lower , P = 0.007), BUB1 (5.6-fold lower, P =0.0047), and SPAG5 (5.4-fold decrease, P = 0.0178) (accession #: GSE18798) (Fig. S1). Furthermore, 15 genes for key regulatory proteins with anti-proliferative functions for example DUSP1 (3.7-fold boost, P = 0.0005), SEPT4 (1.9-fold boost, P =0.018), SEPT7 (1.7-fold boost, P = 0.019), and GAS1 (two.4-fold increase, P = 0.034) showed a moderate improve in expression right after SYK induction (Fig. S1). The serine/threonine kinase ATM, encoded by the Ataxia telangiectasia-mutated (ATM) gene, is activated by DNA damage (viz.: double-stranded DNA breaks) and is essential for G2 checkpoint activation, which is responsible for inhibition of G2/M transition following DNA harm (Innes et al., 2006; Stracker et al., 2008). Within this context, ATM signaling delays the entry into mitosis by causing inactivation of CDC25C and thereby enforces the G2 checkpoint. ATM-dependent G2 checkpoint activation in irradiated mouse cells is associated with down-regulation of a special group of very correlated genes. Notably, the human homologs of lots of ATM-responsive G2 checkpoint signature genes have been also down-regulated by induction of SYK expression in human U373 cells (Fig. 2f g). A cluster of 2 genes (AURKA and CCNB1) showed greater than 5-fold decrease, a cluster of 3 genes (CKS2, GAP43, NCAPD2) showed greater than three.5-fold decrease along with a cluster of three genes (HMGB2, FOXM1, N.