The Involvement of MAPK Signaling Pathways in Determining the Cellular Response to p53 Activation CELL CYCLE ARREST OR APOPTOSIS

摘要: The effect of ERK, p38, and JNK signaling on p53-dependent apoptosis cell cycle arrest was investigated using a Friend murine erythroleukemia virus (FVP)-transformed line that expresses temperature-sensitive p53 allele, DP16.1/p53ts. In response to activation at 32 degrees C, DP16.1/p53ts cells undergo G(1) apoptosis. As result viral transformation, these express the spleen focus forming env-related glycoprotein gp55, which can bind erythropoietin receptor (EPO-R) mimics many aspects EPO-induced EPO-R signaling. We demonstrate p38 mitogen-activated protein kinases (MAPKs) are constitutively active in cells. Constitutive MEK activity contributes phosphorylation serine residue 15. pro-apoptotic this MAPK kinase signal likely reflects an aberrant Ras proliferative arising from FVP-induced transformation. Inhibition alters cellular arrest, with concomitant increase p21(WAF1), suggesting Ras/MEK pathway may influence activation. is anti-apoptotic capable limiting C. Moreover, facilitates turnover, could account for enhanced apoptotic effects inhibiting Overall, data show intrinsic pathways, transformed cells, both positively negatively apoptosis, illustrate their potential affect cancer therapies aimed reconstituting or activating function.