Pluripotent stem cells (PSCs) are an important model system for studying early embryonic developmental processes of both normal and diseased organisms. Furthermore, investigating and revealing the mechanisms that govern PSC biology will be fundamental for their eventual use for therapeutic replacement of defective and/or damaged tissues.Examination of the myelocytomatosis oncogene (MYC) family of transcription factors revealed regulation of a set of target genes that are critical for PSC maintenance, termed the dual-specificity phosphatases (DUSPs). The importance of MYC to PSC biology was previously attributed mainly to its role in activating genes involved in increased metabolism and proliferation. Here I demonstrated that the protein products of MYC genes activates expression of two DUSP family members, DUSP2 and DUSP7, which consequently inhibit activation of mitogen-activated protein kinase - extracellular signal-regulated kinases (MAPK/ERK) signaling, a key determinant of PSC differentiation. This finding demonstrates that the significance of MYC in PSC biology is more nuanced than activation of growth promoting genes.