Interaction of Brn3a and HIPK2 Mediates Transcriptional Repression of Sensory Neuron Survival

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2004 Oct 20

PMID 15492043

Citations 50

Authors

Amanda K Wiggins

Guangwei Wei

Epaminondas Doxakis

Connie Wong

Amy A Tang

Keling Zang

Esther J Luo

Rachael L Neve

Louis F Reichardt

Eric J Huang

Affiliations

Soon will be listed here.

Abstract

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.

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