Trim11 modulates the function of neurogenic transcription factor Pax6 through ubiquitin–proteosome system
- 15 July 2008
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 22 (14), 1972-1986
- https://doi.org/10.1101/gad.471708
Abstract
The transcription factor Pax6 is an important developmental regulator. Spatiotemporal control of Pax6 expression during embryogenesis is crucial for regulating distinct aspects of cortical development. Here, we report that Trim11, a member of the TRIM/RBCC protein family of E3 ubiquitin ligases, interacts with Pax6 and mediates Pax6 degradation via the ubiquitin–proteasome system. Trim11 overexpression decreases endogenous Pax6 protein levels and represses Pax6 functions, including Pax6-dependent transactivation and neurogenesis. Abrogation of endogenous Trim11 expression in the developing cortex increases the level of insoluble forms of Pax6 and enhances apoptosis. We provide evidence that the B30.2 domain of Trim11 is essential for the clearance of insoluble cell proteins. Furthermore, we show that the expression of Trim11 is directly regulated by Pax6 in developing cortex in vivo. Our findings indicate that an autoregulatory feedback loop between Trim11 and Pax6 maintains a balance between the levels of Pax6 and Trim11 proteins in cortical progenitors, having an essential role for the Pax6-dependent neurogenesis.Keywords
This publication has 51 references indexed in Scilit:
- Er81is a downstream target of Pax6 in cortical progenitorsBMC Developmental Biology, 2008
- Controlled overexpression of Pax6 in vivo negatively autoregulates thePax6locus, causing cell-autonomous defects of late cortical progenitor proliferation with little effect on cortical arealizationDevelopment, 2007
- Pax6 controls cerebral cortical cell number by regulating exit from the cell cycle and specifies cortical cell identity by a cell autonomous mechanismDevelopmental Biology, 2006
- Impaired neurogenesis and cardiovascular development in mice lacking the E3 ubiquitin ligases UBR1 and UBR2 of the N-end rule pathwayProceedings of the National Academy of Sciences of the United States of America, 2006
- Molecular mechanisms of cortical differentiationEuropean Journal of Neuroscience, 2006
- Ubiquitin C-terminal hydrolase L1 regulates the morphology of neural progenitor cells and modulates their differentiationJournal of Cell Science, 2006
- Ubiquitin-binding domainsNature Reviews Molecular Cell Biology, 2005
- Modulation of neurodegeneration by molecular chaperonesNature Reviews Neuroscience, 2005
- A polyalanine tract expansion in Arx forms intranuclear inclusions and results in increased cell deathThe Journal of cell biology, 2004
- Mouse Small eye results from mutations in a paired-like homeobox-containing geneNature, 1991