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Title

Encoding Mash1 suppresses MYCN mitotic activity

AuthorsÁlvarez-Rodríguez, Rubén; Pons, Sebastián
KeywordsMYCN
Mash1
Cyclin D2
Proneural
Oncogene
Cerebellar granular neuronal precursors
Issue Date10-Feb-2009
PublisherCompany of Biologists
CitationJournal of Cell Science 122(4): 595-599 (February 2009)
AbstractMurine Mash1 (Ascl1) is a member of the basic helix-loop-helix family of transcription factors and has been described to promote differentiation in some neural precursors. The process of differentiation is coordinated with a concomitant cell-cycle arrest, but the molecular mechanism of this process is unclear. Here, we describe for the very first time a direct regulation of an oncogene by a proneural gene. When expressed in proliferating cerebellar granular precursors, expression of the proneural gene encoding Mash1 promotes cell-cycle exit and differentiation, whereas expression of the oncogene MYCN has the opposite effect, promotingthe proliferation of these cells in the absence of sonic hedgehog. Moreover, Mash1 overexpression neutralizes MYCN-induced proliferation. We now propose that the mechanism of antagonism between both molecules is based on opposite functions in the transcriptional regulation of the E-box motif, particularly in the E-boxes within the cyclin-D2 promoter, with MYCN acting as a transcriptional activator and Mash1 as a repressor. In agreement with this result, overexpression of cyclin D2 suppressed the anti-proliferative activity of Mash1.
Publisher version (URL)http://dx.doi.org/10.1242/jcs.037556
URIhttp://hdl.handle.net/10261/31616
DOI10.1242/jcs.037556
ISSN0021-9533
E-ISSN1477-9137
Appears in Collections:(IIBB) Artículos
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