Mehta et al. (2011) extend this observation by uncovering that Olig2 becomes dispensable for

tumor formation in the absence of p53. Furthermore, Sun et al. (2011) have found that the triple-serine motif is highly phosphorylated in several glioma lines and that the phosphomimetic Olig2 protein is even Ponatinib price more tumorigenic than the wild-type protein. These findings together strongly support the authors’ contention that the ability of Olig2 to promote neural stem and progenitor cell proliferation is mediated through its opposition to the p53 pathway and that this mechanism contributes to the pathology of many human gliomas. While the Sun and Mehta studies provide important new insights into the role of Olig2 in tumor formation, many questions remain unresolved. First, how does the phosphorylation of the triple-serine motif alter Olig2 interactions Carfilzomib concentration with regulators of p53 and other pathways? Second, how prevalent is the Olig2-mediated suppression of p53 within human gliomas? Although Sun et al. (2011) report that Olig2 was phosphorylated in several glioma samples, a more systematic survey is needed to determine the

generality of this proposed mechanism for glioma pathogenesis and assess its implications for human disease. Third, what are the kinases and phosphatases that act upon the triple-serine motif, and how are they regulated? Finally, could the S147 and triple-serine phosphorylation events be combined to further expand the diversity of Olig2′s function in the nervous system? In summary, these papers provide an elegant example of

how developmentally regulated phosphorylation events endow Olig2 with its unique biological functions. The findings further suggest a general strategy through which posttranslational modifications can enable single transcription factors to be co-opted for Carnitine palmitoyltransferase II different purposes. Moreover, the correlation of Olig2 phosphorylation at the triple-serine motif with human gliomas make the removal of this modification a very promising avenue for the development of new therapies to combat glial tumor growth. “
“Seventeen years ago a quiet revolution in neuroscience began with the discovery that astrocytes, the major subtype of glia, could excite and activate neighboring neurons (Nedergaard, 1994 and Parpura et al., 1994). One of these studies demonstrated the importance of the astrocytic release of the chemical transmitter glutamate (Parpura et al., 1994) in a process that has been termed gliotransmission. This observation, initially demonstrated in culture, moved to brain slice studies and more recently in vivo. In this issue of Neuron, Andrea Volterra and colleagues ( Santello et al., 2011) now show that the presence of proinflammatory cytokine TNFα acts as a state-dependent switch to control the functional nature of gliotransmission.