Science Signaling Podcast: 24 March 2015

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Sci. Signal.  24 Mar 2015:
Vol. 8, Issue 369, pp. pc7
DOI: 10.1126/scisignal.aab0961

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This Podcast features an interview with Tilman Borggrefe, author of a Research Article that appears in the 24 March 2015 issue of Science Signaling, about a posttranslational modification of the receptor Notch that targets the receptor for degradation. The Notch signaling pathway is involved in many developmental processes, and its misregulation has been implicated in several types of cancer. Upon ligand binding, Notch is proteolytically cleaved, and the Notch intracellular domain (NICD) is released into the cytoplasm. NICD then translocates into the nucleus, where it cooperates with transcription factors to activate gene expression. Several posttranslational modifications that affect the stability of Notch, and therefore its ability to transduce signaling, have been characterized. Hein et al. discovered that methylation promotes degradation of Notch and that this modification is specifically required to mediate short periods of transient Notch signaling during embryonic development. Mutant forms of Notch that cannot be methylated may contribute to dysregulation of Notch signaling in cancer.

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