First Author | Lu CK | Year | 2012 |
Journal | Biochem Biophys Res Commun | Volume | 418 |
Issue | 2 | Pages | 307-12 |
PubMed ID | 22266316 | Mgi Jnum | J:181286 |
Mgi Id | MGI:5310696 | Doi | 10.1016/j.bbrc.2012.01.016 |
Citation | Lu CK, et al. (2012) CCAR1 is required for Ngn3-mediated endocrine differentiation. Biochem Biophys Res Commun 418(2):307-12 |
abstractText | Neurogenin3 (Ngn3) is a basic helix-loop-helix transcription factor that specifies pancreatic endocrine cell fates during pancreas development. It can also initiate a transdifferentiation program when expressed in pancreatic exocrine and ductal cells. However, how Ngn3 initiates a transcriptional cascade to achieve endocrine differentiation is still poorly understood. Here, we show that cell cycle and apoptosis regulator 1 (CCAR1), which is a transcriptional coactivator for nuclear receptors, also interacts with Ngn3. The association between Ngn3 and CCAR1 was verified by pull-down assays and co-immunoprecipitation analyses. Using gene reporter assays, we found that CCAR1 is essential for Ngn3 to activate the expression of the reporter genes containing the NeuroD promoter. Moreover, down-regulation of endogenous CCAR1 in the PANC-1 pancreatic ductal cell line inhibits the transdifferentiation program initiated by Ngn3. CCAR1 is, therefore, a novel partner of Ngn3 in mediating endocrine differentiation. |