Two conserved domains in PCIF1 mediate interaction with pancreatic transcription factor PDX-1.

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.
Mesh Terms:
Amino Acid Motifs, Amino Acid Sequence, Animals, Cell Nucleus, Conserved Sequence, Evolution, Molecular, Glutamine, HeLa Cells, Homeodomain Proteins, Humans, Lysine, Mice, Molecular Sequence Data, Mutation, Nuclear Proteins, Pancreas, Protein Binding, Protein Structure, Tertiary, Protein Transport, Repressor Proteins, Trans-Activators, Transcription Factors, Transcriptional Activation, Zebrafish
FEBS Lett.
Date: Dec. 11, 2006
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