Neural precursor cycling at sonic speed: N-Myc pedals, GSK-3 brakes Journal Article
| Authors: | Knoepfler, P. S.; Kenney, A. M. |
| Article Title: | Neural precursor cycling at sonic speed: N-Myc pedals, GSK-3 brakes |
| Abstract: | Signaling by the sonic hedgehog (Shh) pathway is essential for neural precursor population expansion during normal central nervous system (CNS) development, and is implicated in the childhood brain tumor, medulloblastoma. the proto-oncogene N-myc plays essential roles as a downstream effector of Shh proliferative effects in neural precursors of the cerebellum, where medulloblastomas arise. It is likely that N-Myc has analogous functions in medulloblastomas and other CNS tumors where it is highly expressed due to altered regulation or gene amplification. Myc destabilization occurs in response to phosphorylation by GSK-3β. N-Myc degradation is required for cerebellar neural precursors to exit the cell cycle. During mitosis in cerebellar neural precursors, levels of N-Myc primed for phosphorylation by GSK-3βincrease, due to cdk1 complex activity towards N-Myc. GSK-3β is kept in check by insulin-like growth factor signaling, which also plays critical roles in brain development and cancer. These findings indicate that therapeutic strategies targeting N-myc and the IGF pathway might be effective against medulloblastoma. ©2006 Landes Bioscience. |
| Keywords: | signal transduction; somatomedin; protein phosphorylation; review; nonhuman; brain tumor; protein function; mitosis; animals; cerebellum; cell cycle; gene amplification; gene expression; cell maturation; enzyme degradation; sonic hedgehog protein; hedgehog proteins; gene function; cell differentiation; neurons; enzyme activity; central nervous system; time factors; cell culture; brain development; medulloblastoma; stem cells; cell count; trans-activators; proto-oncogene proteins c-myc; erinaceidae; oncogene c myb; growth disorder; velocity; cyclin dependent kinase activating kinase; glycogen synthase kinase 3; n-myc; progenitor cells; insulin-like growth factor |
| Journal Title: | Cell Cycle |
| Volume: | 5 |
| Issue: | 1 |
| ISSN: | 1538-4101 |
| Publisher: | Taylor & Francis Inc. |
| Date Published: | 2006-01-01 |
| Start Page: | 47 |
| End Page: | 52 |
| Language: | English |
| PUBMED: | 16322694 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 48" - "Export Date: 4 June 2012" - "Source: Scopus" |
