| First Author | Liu A | Year | 2006 |
| Journal | FEBS Lett | Volume | 580 |
| Issue | 28-29 | Pages | 6701-6 |
| PubMed ID | 17126328 | Mgi Jnum | J:201256 |
| Mgi Id | MGI:5512841 | Doi | 10.1016/j.febslet.2006.11.021 |
| Citation | Liu A, et al. (2006) Two conserved domains in PCIF1 mediate interaction with pancreatic transcription factor PDX-1. FEBS Lett 580(28-29):6701-6 |
| abstractText | PCIF1 is a TRAF and POZ domain containing nuclear factor that interacts with and inhibits transactivation of pancreatic homeodomain transcription factor PDX-1. Here, we demonstrate interaction of endogenous PDX-1 and PCIF1 in MIN6 insulinoma cells. Within PCIF1, the TRAF and POZ domains are both required for physical and functional interaction with the C-terminus of PDX-1, whereas the C-terminal domain of PCIF1 directs its nuclear localization. A human PDX-1 mutation associated with diabetes, E224K, disrupts the ability of PCIF1 to inhibit PDX-1 transactivation, suggesting that the interaction between PDX-1 and PCIF1 is required for normal glucose homeostasis. Inhibition of transactivation occurs by a mechanism distinct from the classical role of POZ domains to recruit co-repressors and histone deacetylases. Understanding the functional roles of PCIF1 domains may have application to therapeutic beta-cell replacement strategies involving PDX-1 for the treatment of diabetes. |
