Tumor suppressor BLU exerts growth inhibition by blocking ERK signaling and disrupting cell cycle progression through RAS pathway interference.

We have previously reported that the 3p21 tumor suppressor regulates cell cycle by blocking JNK/MAPK signaling. Another member of the MAPK family, extracellular signal response kinase (ERK), is induced by the RAS-RAF-MEK-ERK pathway and is targeted in anticancer therapy. The effects of on tumor growth were evaluated by measuring the size of nasopharyngeal carcinoma (NPC) xenografted tumors intra-tumorally injected with adenovirus 5 ( Ad5) and the viability of NPC cells transferred with . Tumor size was correlated with downregulation of the ERK pathway by . Phosphorylation of ERK and Elk reporter activities were assayed. The regulated cyclins D1 and B1 were measured by and gene promoter activity by co-transfection of , V12G, together with . The cell cycle phase distribution was determined by FACS-based DNA content assay. The data showed that growth of the xenografted tumor was inhibited and viability of HONE-1 cells was reduced by recombinant . down-regulated ERK signaling by reducing protein substrate phosphorylation, inhibiting Elk reporter activity, and blocking promoter activities of the gene and reduced cyclins D1 expression to arrest the cell cycle at the G1 phase. The population of G2/M cells was also remarkably decreased. activated ERK and cyclin D1 and B1 promoters, and the effects were antagonized by . Taken together, our results suggested that inhibited ERK signaling, downregulated cyclins D1 and B1, and prevented cell cycle progression through interfering with signaling to exert tumor suppression.