Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1384489 (Scratch)
 395 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Members of the Snail family of zinc finger transcription factors are known to play critical roles in neurogenesis in invertebrates, but none of these factors has been linked to vertebrate neuronal differentiation. We report the isolation of a gene encoding a mammalian Snail family member that is restricted to the nervous system. Human and murine Scratch (Scrt) share 81% and 69% identity to Drosophila Scrt and the Caenorhabditis elegans neuronal antiapoptotic protein, CES-1, respectively, across the five zinc finger domain. Expression of mammalian Scrt is predominantly confined to the brain and spinal cord, appearing in newly differentiating, postmitotic neurons and persisting into postnatal life. Additional expression is seen in the retina and, significantly, in neuroendocrine (NE) cells of the lung. In a parallel fashion, we detect hScrt expression in lung cancers with NE features, especially small cell lung cancer. hScrt shares the capacity of other Snail family members to bind to E-box enhancer motifs, which are targets of basic helix--loop--helix (bHLH) transcription factors. We show that hScrt directly antagonizes the function of heterodimers of the proneural bHLH protein achaete-scute homolog-1 and E12, leading to active transcriptional repression at E-box motifs. Thus, Scrt has the potential to function in newly differentiating, postmitotic neurons and in cancers with NE features by modulating the action of bHLH transcription factors critical for neuronal differentiation.
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PMID:Mammalian Scratch: a neural-specific Snail family transcriptional repressor. 1127 25

Mammalian Scratch (Scrt) is a Snail family zinc finger transcription factor that is specifically expressed in newly differentiating, post-mitotic central nervous system neurons. While Scrt-related genes appear essential for invertebrate neurogenesis, the role of Scrt in mammalian neural development is unknown. In this study, we found that neural differentiation of multipotent mouse P19 embryonal carcinoma cells by retinoic acid led to the appearance of Scrt together with neuron-specific class III beta-tubulin (Tuj1), following the earlier elaboration of Mash1. Transient co-transfection in P19 cells with either Mash1 or NeuroD2 plus E12 also induced Scrt gene expression. Moreover, overexpression of Scrt alone was sufficient to confer Tuj1 immunoreactivity and neuronal morphology in a subset of P19 cells. Scrt thus appears to function downstream of proneural bHLH proteins in promoting mammalian neural differentiation in this model system.
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PMID:Mammalian Scratch participates in neuronal differentiation in P19 embryonal carcinoma cells. 1168 88