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PMID:19269368

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Citation

Schwamborn, JC, Berezikov, E and Knoblich, JA (2009) The TRIM-NHL protein TRIM32 activates microRNAs and prevents self-renewal in mouse neural progenitors. Cell 136:913-25

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.

Links

PubMed PMC2988196 Online version:10.1016/j.cell.2008.12.024

Keywords

Animals; Cell Differentiation; Cell Proliferation; Mice; MicroRNAs/metabolism; Neurogenesis; Neurons/cytology; Neurons/metabolism; Proto-Oncogene Proteins c-myc/metabolism; Stem Cells/cytology; Stem Cells/metabolism; Ubiquitin-Protein Ligases/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:MYC

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8CH72

F

Seeded From UniProt

complete

MOUSE:TRI32

enables

GO:0061630: ubiquitin protein ligase activity

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(MGI:MGI:97250)

Seeded From UniProt

complete

MOUSE:TRI32

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P01108

F

Seeded From UniProt

complete

MOUSE:TRI32

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8CJG1

F

Seeded From UniProt

complete

MOUSE:TRI32

involved_in

GO:0016567: protein ubiquitination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TRI32

enables

GO:0003723: RNA binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:TRI32

involved_in

GO:0050769: positive regulation of neurogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TRI32

involved_in

GO:0048147: negative regulation of fibroblast proliferation

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TRI32

involved_in

GO:0045732: positive regulation of protein catabolic process

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TRI32

involved_in

GO:0045666: positive regulation of neuron differentiation

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:TRI32

enables

GO:0061630: ubiquitin protein ligase activity

ECO:0000314: direct assay evidence used in manual assertion

F

  • has_input:(UniProtKB:P01108)

Seeded From UniProt

complete

MOUSE:AGO1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q8CH72

F

Seeded From UniProt

complete


See also

References

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