Regulation of p53 and hid by Phosphorylated MAP Kinase in Developing Eye of Drosophila

Abstract

Mitogen Activated Protein Kinase (MAP Kinase) pathway regulates many diverse cellular processes including cell division, growth and differentiation. Many proteins are involved in this complex mechanism of cell cycle regulation. Any mutation in one or more of these proteins may results in abnormal cell phenotypes including tumor formation. Phosphorylated MAPK (dpMAPK/dpERK) is a key protein activated downstream of Ras (proto-oncogene), and regulates cell divison and differentiation depending on whether MAPK is localized in the nucleus or cytoplasm respectively. Earlier it was reported that nuclear localization of non-phosphorylated MAPK (ERK) is another novel mechanism which may initiate cell division in the developing eye of Drosophila. However, phosphorylation of MAPK is required for proper cell differentiation and growth. Here we conducted a study on the expression pattern of p53 (tumor suppressor protein) in absence of phosphorylated MAPK. We also studied effect of hid (death activating protein) on MAPK activation and p53 gene expression. Our study shows that active MAPK is required for p53 gene expression. Moreover, we report here for the first time a new mode of negative regulation of p53 gene expression by the nuclear form of non-phosphorylated MAPK (MAPK-nls). Our studies also suggest that presence of hid may induce activation of MAPK via an unknown protein kinase. Mutations in MAPK and p53 have been reported in most human tumors. Inhibition of Ras/MAPK is used as a mechanism for controlling tumor growth by many cancer drugs. Considering all these together our study might provide valuable contribution to design novel cancer drug.