| First Author | Wiggins AK | Year | 2004 |
| Journal | J Cell Biol | Volume | 167 |
| Issue | 2 | Pages | 257-67 |
| PubMed ID | 15492043 | Mgi Jnum | J:93311 |
| Mgi Id | MGI:3056843 | Doi | 10.1083/jcb.200406131 |
| Citation | Wiggins AK, et al. (2004) Interaction of Brn3a and HIPK2 mediates transcriptional repression of sensory neuron survival. J Cell Biol 167(2):257-67 |
| abstractText | 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. |
