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Working with two clones of chromaffin\u2013neuronal PC12 cells, which express different levels of REST, and using genetic complementation and knockdown approaches, we show that REST also promotes proliferation in differentiated neural cells. Mechanistically, this occurs by a signaling pathway involving REST, the GTPase-activating protein tuberin (TSC2) and the transcription co-factor \u03b2-catenin. In PC12 cells, raised expression of REST correlates with reduced TSC2 levels, nuclear accumulation and co-transcriptional activation of \u03b2-catenin, and increased expression of its target oncogenes Myc and Ccnd1, which might account for the proliferation advantage and the distinct morphology. Rest transcription is also increased, unveiling the existence of a self-sustaining, feed-forward REST\u2013TSC2\u2013\u03b2-catenin signaling loop that is also operative in another neural cell model, NT2\/D1 cells. Transfection of REST, knockdown of TSC2 or forced expression of active \u03b2-catenin recapitulated the biochemical, functional and morphological properties of the high-expressing REST clone in wild-type PC12 cells. Upregulation of REST promoted proliferation and phenotypic changes, thus hindering neurosecretion. The new REST\u2013TSC2\u2013\u03b2-catenin signaling paradigm might have an important role in various aspects of neural cell physiology and pathology, including the regulation of proliferation and neurosecretion.<\/jats:p>","DOI":"10.1242\/jcs.087551","type":"journal-article","created":{"date-parts":[[2011,8,25]],"date-time":"2011-08-25T03:15:49Z","timestamp":1314242149000},"page":"3174-3186","source":"Crossref","is-referenced-by-count":26,"title":["A signaling loop of REST, TSC2 and \u03b2-catenin governs proliferation and function of PC12 neural cells"],"prefix":"10.1242","volume":"124","author":[{"given":"Romana","family":"Tomasoni","sequence":"first","affiliation":[{"name":"Division of Immunology, Transplantation\/Infectious Diseases, San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy"},{"name":"Vita-Salute San Raffaele University, Via Olgettina 58, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Negrini","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy"},{"name":"IIT Network, Research Unit of Molecular Neuroscience, Via Olgettina 58, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Fiordaliso","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy"},{"name":"IIT Network, Research Unit of Molecular Neuroscience, Via Olgettina 58, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrijana","family":"Klajn","sequence":"additional","affiliation":[{"name":"Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 444a Vojvode Stepe Str., PO Box 23, 11010 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Tkatch","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Brain Technologies, Italian Institute of Technology, Via Morego 30, 16163 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Mondino","sequence":"additional","affiliation":[{"name":"Division of Immunology, Transplantation\/Infectious Diseases, San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacopo","family":"Meldolesi","sequence":"additional","affiliation":[{"name":"Vita-Salute San Raffaele University, Via Olgettina 58, 20132 Milan, Italy"},{"name":"Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy"},{"name":"IIT Network, Research Unit of Molecular Neuroscience, Via Olgettina 58, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalba","family":"D'Alessandro","sequence":"additional","affiliation":[{"name":"Division of Neuroscience, San Raffaele Scientific Institute, Via Olgettina 58, 20132 Milan, Italy"},{"name":"IIT Network, Research Unit of Molecular Neuroscience, Via Olgettina 58, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042521360145900_R1","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.neuron.2007.01.016","article-title":"NMDA-receptor activation induces calpain-mediated \u03b2-catenin cleavages for triggering gene expression","volume":"53","author":"Abe","year":"2007","journal-title":"Neuron"},{"key":"2021042521360145900_R2","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/0012-1606(84)90316-6","article-title":"Retinoic acid induces neuronal differentiation of a cloned human embryonal carcinoma cell line in vitro","volume":"103","author":"Andrews","year":"1984","journal-title":"Dev. Biol."},{"key":"2021042521360145900_R3","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.conb.2005.08.015","article-title":"The many faces of REST oversee epigenetic programming of neuronal genes","volume":"15","author":"Ballas","year":"2005","journal-title":"Curr. Opin. Neurobiol."},{"key":"2021042521360145900_R4","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1165\/rcmb.2008-0335OC","article-title":"The loss of tuberin promotes cell invasion through the \u03b2-catenin pathway","volume":"43","author":"Barnes","year":"2010","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2021042521360145900_R5","doi-asserted-by":"crossref","first-page":"10458","DOI":"10.1073\/pnas.0401827101","article-title":"Genome-wide analysis of repressor element1 silencing transcription factor\/neuron-restrictive silencing factor (REST\/NRSF) target genes","volume":"101","author":"Bruce","year":"2004","journal-title":"Proc. Natl. Acad. Sci. 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Physiol."},{"key":"2021042521360145900_R9","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/nchembio.137","article-title":"Small molecule-mediated disruption of Wnt-dependent signaling in tissue regeneration and cancer","volume":"5","author":"Chen","year":"2009","journal-title":"Nat. Chem. Biol."},{"key":"2021042521360145900_R10","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1126\/science.1074192","article-title":"Regulation of cerebral cortical size by control of cell cycle exit in neural precursors","volume":"297","author":"Chenn","year":"2002","journal-title":"Science"},{"key":"2021042521360145900_R11","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1016\/S0169-328X(00)00058-9","article-title":"Wnt-1 inhibits nerve growth factor-induced differentiation of PC12 cells by preventing the induction of some, but not all, late response genes","volume":"77","author":"Chou","year":"2000","journal-title":"Brain Res. Mol. 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Chem."},{"key":"2021042521360145900_R38","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/j.1469-7793.1999.t01-1-00043.x","article-title":"Neurosecretory cells without neurosecretion: evidence of an independently regulated trait of the cell phenotype","volume":"520","author":"Malosio","year":"1999","journal-title":"J. Physiol."},{"key":"2021042521360145900_R39","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/j.molcel.2008.10.025","article-title":"CDYL bridges REST and histone methyltransferases for gene repression and suppression of cellular transformation","volume":"32","author":"Mulligan","year":"2008","journal-title":"Mol. Cell"},{"key":"2021042521360145900_R40","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1038\/nn.2477","article-title":"Tsc2-Rheb signaling regulates EphA-mediated axon guidance","volume":"13","author":"Nie","year":"2010","journal-title":"Nat. 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