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StIP‐1/Elp2 regulation of DeltaF508‐CFTR vesicular exocytosis and of HSP70 expression
Author(s) -
Suaud Laurence,
Rubenstein Ronald C
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.1000.14
Subject(s) - chemistry , golgi apparatus , microbiology and biotechnology , cystic fibrosis transmembrane conductance regulator , exocytosis , biology , endoplasmic reticulum , biochemistry , gene , secretion
Sodium 4‐Phenylbutyrate (4PBA) improves the intracellular trafficking of deltaF508‐CFTR in Cystic Fibrosis (CF) epithelial cells. In IB3‐1 CF bronchiolar epithelial cells, 1 mM 4PBA transiently increases the expression of StIP‐1, a STAT‐3 interacting protein. StIP‐1 is identical to Elongator protein 2 (Elp2); Elongator is a protein complex that facilitates mRNA transcription by RNA polymerase II. In immunofluorescence experiments, overexpression of StIP‐1 in IB3‐1 cells increased deltaF508‐CFTR trafficking to the plasma membrane even in the absence of 4PBA treatment. In contrast, overexpression of a mutant of StIP‐1 blocked the 4PBA‐stimulated improvement of deltaF508‐CFTR trafficking. StIP‐1 was observed to colocalize with a 58k golgi protein (Golgi marker) as well as with Snap25/23 (vesicle trafficking marker). These data suggest that StIP‐1 may regulate deltaF508‐CFTR trafficking along the exocytic pathway. As Elongator also directly regulated Hsp70 expression in yeast (Hanq et al., 2007), we tested whether StIP‐1/Elp2 regulates Hsp70 expression, which may regulate deltaF508 trafficking. In T84 cells transfected with siRNA targeting StIP‐1/Elp2, StIP‐1/Elp2 protein expression was reduced by about 50% and Hsp70 expression was reduced by 80% compared with control cells. These data suggest that StIP‐1/Elp2 may also influence deltaF508‐CFTR trafficking by regulating HSP 70 expression.