β-arrestin-1 links mitogenic sonic hedgehog signaling to the cell cycle exit machinery in neural precursors Journal Article


Authors: Parathath, S. R.; Mainwaring, L. A.; Fernandez-L, A.; Guldal, C. G.; Nahlé, Z.; Kenney, A. M.
Article Title: β-arrestin-1 links mitogenic sonic hedgehog signaling to the cell cycle exit machinery in neural precursors
Abstract: Development of the cerebellum, a brain region regulating posture and coordination, occurs post-natally and is marked by rapid proliferation of granule neuron precursors (CGNPs), stimulated by mitogenic Sonic hedgehog (Shh) signaling. β-Arrestin (βArr) proteins play important roles downstream of Smoothened, the Shh signal transducer. However, whether Shh regulates βArrs and what role they play in Shh-driven CGNP proliferation remains to be determined. Here, we report that Shh induces βArr1 accumulation and localization to the nucleus, where it participates in enhancing expression of the cyclin dependent kinase (cdk) inhibitor p27, whose accumulation eventually drives CGNP cell cycle exit. βArr1 knockdown enhances CGNP proliferation and reduces p27 expression. Thus, Shh-mediated βArr1 induction represents a novel negative feedback loop within the Shh mitogenic pathway, such that ongoing Shh signaling, while required for CGNPs to proliferate, also sets up a cell-intrinsic clock programming their ultimate exit from the cell cycle. © 2010 Landes Bioscience.
Keywords: signal transduction; protein expression; nonhuman; protein function; protein localization; cell proliferation; mitosis; animal cell; mouse; animals; mice; animal tissue; cerebellum; cells, cultured; cell cycle; sonic hedgehog protein; mitogenesis; hedgehog proteins; regulatory mechanism; promoter regions, genetic; cyclin dependent kinase inhibitor 1b; cyclin-dependent kinase inhibitor p27; newborn; protein induction; negative feedback; cell cycle phase; neural stem cells; sonic hedgehog; erinaceidae; differentiation; cyclic amp response element-binding protein; jnk mitogen-activated protein kinases; p27; β-arrestin 1; neural precursor; beta arrestin 1; nerve cell stimulation; arrestins; p300-cbp transcription factors
Journal Title: Cell Cycle
Volume: 9
Issue: 19
ISSN: 1538-4101
Publisher: Taylor & Francis Inc.  
Date Published: 2010-10-01
Start Page: 4013
End Page: 4024
Language: English
DOI: 10.4161/cc.9.19.13325
PUBMED: 20935513
PROVIDER: scopus
PMCID: PMC3047755
DOI/URL:
Notes: --- - "Export Date: 20 April 2011" - "Source: Scopus"
Altmetric
Citation Impact
MSK Authors
  1. Cemile Gokce Guldal
    6 Guldal
  2. Anna Marie Kenney
    34 Kenney