title: From cerebellar proliferation to tumorigenesis: new insights into the role of Mad3.
abstract: During development, Sonic hedgehog (Shh) regulates the proliferation of cerebellar granule neuron precursors (GNPs) in part via expression of Nmyc. Mutations in the Shh signaling pathway lead to brain tumors in mice and humans. We have recently identified a novel role for the Mad family member Mad3 in GNP proliferation and Nmyc expression. Interestingly, Mad3 expression is upregulated in mouse models of medulloblastoma, the most common brain tumor in children. These results are surprising because current models suggest that Mad proteins should antagonize Myc proteins by competition for direct DNA binding via Max heterodimerization to inhibit cellular proliferation and potentially tumor progression. Here, we discuss our recent work in the context of candidate Mad3-interacting proteins and Mad3 expression in human brain tumors that together suggest interesting insights into the role of Mad3 in cellular proliferation and tumorigenesis.
authors.affiliation: Department of Pharmacology, UC Davis School of Medicine, Davis, California 95616, USA.
authors.forename: Gustavo A
authors.initials: GA
authors.lastname: Barisone
authors.forename: Jun-Soo
authors.initials: JS
authors.lastname: Yun
authors.forename: Elva
authors.initials: E
authors.lastname: Díaz
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002531:Cerebellum / Q000166:cytology* / Q000254:growth & development; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D008527:Medulloblastoma / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D053823:Hedgehog Proteins; C472089:Mxd3 protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; C465570:Shh protein, mouse