RGD Reference Report - Interaction of Brn3a and HIPK2 mediates transcriptional repression of sensory neuron survival. - Rat Genome Database

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Interaction of Brn3a and HIPK2 mediates transcriptional repression of sensory neuron survival.

Authors: Wiggins, AK  Wei, G  Doxakis, E  Wong, C  Tang, AA  Zang, K  Luo, EJ  Neve, RL  Reichardt, LF  Huang, EJ 
Citation: Wiggins AK, etal., J Cell Biol 2004 Oct 25;167(2):257-67. Epub 2004 Oct 18.
RGD ID: 1302930
Pubmed: PMID:15492043   (View Abstract at PubMed)
PMCID: PMC2172556   (View Article at PubMed Central)
DOI: DOI:10.1083/jcb.200406131   (Journal Full-text)

The Pit1-Oct1-Unc86 domain (POU domain) transcription factor Brn3a controls sensory neuron survival by regulating the expression of Trk receptors and members of the Bcl-2 family. Loss of Brn3a leads to a dramatic increase in apoptosis and severe loss of neurons in sensory ganglia. Although recent evidence suggests that Brn3a-mediated transcription can be modified by additional cofactors, the exact mechanisms are not known. Here, we report that homeodomain interacting protein kinase 2 (HIPK2) is a pro-apoptotic transcriptional cofactor that suppresses Brn3a-mediated gene expression. HIPK2 interacts with Brn3a, promotes Brn3a binding to DNA, but suppresses Brn3a-dependent transcription of brn3a, trkA, and bcl-xL. Overexpression of HIPK2 induces apoptosis in cultured sensory neurons. Conversely, targeted deletion of HIPK2 leads to increased expression of Brn3a, TrkA, and Bcl-xL, reduced apoptosis and increases in neuron numbers in the trigeminal ganglion. Together, these data indicate that HIPK2, through regulation of Brn3a-dependent gene expression, is a critical component in the transcriptional machinery that controls sensory neuron survival.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
negative regulation of apoptotic process  TAS 1302930 RGD 
transcription by RNA polymerase II  TAS 1302930 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
DNA binding  TAS 1302930 RGD 
DNA-binding transcription factor activity  TAS 1302930 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pou4f1  (POU class 4 homeobox 1)

Objects referenced in this article
Gene Hipk2 homeodomain interacting protein kinase 2 Mus musculus

Additional Information