| First Author | Friedman ER | Year | 2007 |
| Journal | Biochem Biophys Res Commun | Volume | 363 |
| Issue | 1 | Pages | 113-8 |
| PubMed ID | 17826745 | Mgi Jnum | J:125162 |
| Mgi Id | MGI:3757788 | Doi | 10.1016/j.bbrc.2007.08.108 |
| Citation | Friedman ER, et al. (2007) Separate necdin domains bind ARNT2 and HIF1alpha and repress transcription. Biochem Biophys Res Commun 363(1):113-8 |
| abstractText | PWS is caused by the loss of expression of a set of maternally imprinted genes including NECDIN (NDN). NDN is expressed in post-mitotic neurons and plays an essential role in PWS as mouse models lacking only the Ndn gene mimic aspects of this disease. Patients haploid for SIM1 develop a PW-like syndrome. Here, we report that NDN directly interacts with ARNT2, a bHLH-PAS protein and dimer partner for SIM1. We also found that NDN can interact with HIF1alpha. We showed that NDN can repress transcriptional activation mediated by ARNT2:SIM1 as well as ARNT2:HIF1alpha. The N-terminal 115 residues of NDN are sufficient for interaction with the bHLH domains of ARNT2 or HIF1alpha but not for transcriptional repression. Using GAL4-NDN fusion proteins, we determined that NDN possesses multiple repression domains. We thus propose that NDN regulates neuronal function and hypoxic response by regulating the activities of the ARNT2:SIM1 and ARNT2:HIF1alpha dimers, respectively. |
