Journal
FEBS LETTERS
Volume 580, Issue 28-29, Pages 6701-6706Publisher
WILEY
DOI: 10.1016/j.febslet.2006.11.021
Keywords
diabetes; MODY; pancreas; islet; development; insulin
Funding
- NHLBI NIH HHS [5F31HL071273] Funding Source: Medline
- NIDDK NIH HHS [P30 DK50306, P01 DK49210, R01 DK068157] Funding Source: Medline
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PCIF1 is a TRAF and POZ domain containing nuclear factor that interacts with and inhibits transactivation of pancreatic homeodomain transcription factor PDX-1. He e, 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 historic 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. (c) 2006 Federation of European Biochemical Societies.
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