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PMID: 19269368 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The TRIM-NHL protein TRIM32 activates microRNAs and prevents self-renewal in mouse neural progenitors.

Cell ·Vol. 136 ·No. 5 ·2009-03-06 ·Pages 913-25

Schwamborn JC, Berezikov E, Knoblich JA

Abstract

In the mouse neocortex, neural progenitor cells generate both differentiating neurons and daughter cells that maintain progenitor fate. Here, we show that the TRIM-NHL protein TRIM32 regulates protein degradation and microRNA activity to control the balance between those two daughter cell types. In both horizontally and vertically dividing progenitors, TRIM32 becomes polarized in mitosis and is concentrated in one of the two daughter cells. TRIM32 overexpression induces neuronal differentiation while inhibition of TRIM32 causes both daughter cells to retain progenitor cell fate. TRIM32 ubiquitinates and degrades the transcription factor c-Myc but also binds Argonaute-1 and thereby increases the activity of specific microRNAs. We show that Let-7 is one of the TRIM32 targets and is required and sufficient for neuronal differentiation. TRIM32 is the mouse ortholog of Drosophila Brat and Mei-P26 and might be part of a protein family that regulates the balance between differentiation and proliferation in stem cell lineages.

MeSH Terms
Animals Cell Differentiation Cell Proliferation Mice MicroRNAs/metabolism Neurogenesis Neurons/cytology,metabolism Proto-Oncogene Proteins c-myc/metabolism Stem Cells/cytology,metabolism Ubiquitin-Protein Ligases/metabolism
Chemicals
MicroRNAs Proto-Oncogene Proteins c-myc TRIM32 protein, mouse Ubiquitin-Protein Ligases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Schwamborn Jens C
Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.
Berezikov Eugene
Knoblich Juergen A
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2008.12.024
Published
2009-03-06
Pages
913-25
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2988196
Subset
IM
Grants
Austrian Science Fund FWF · P 16629 · Austria
Corrections
CommentIn
PMID: 19269362
External Links
PubMed source DOI: 10.1016/j.cell.2008.12.024 PMC Full Text View journal details
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