BR22, a novel protein, interacts with thyroid transcription factor-1 and activates the human surfactant protein B promoter

Y. S. Yang, M. C W Yang, B. Wang, J. C. Weissler

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Surfactant protein (SP)-B expression is restricted to type II pneumocytes and Clara cells in the lung. Previously, a promoter region of human SP-B gene from -64 to -118 has been identified as critical for the tissue-specific expression of this gene. Two cis-elements for thyroid transcription factor (TTF)-1 and hepatocyte nuclear factor (HNF)-3α binding were found within this area. Using an oligonucleotide fragment, we incorporated this region sequence into the promoter of a HIS3 reporter gene in yeast. With this modified yeast a human lung complementary DNA (cDNA) library was screened for DNA-binding proteins, other than TTF-1 and HNF-3α, that interacted with this promoter segment. A cDNA clone encoding a novel polypeptide, BR22, was identified that activated the reporter gene expression in yeast. This gene is expressed in many tissues and encodes a protein with bipartite nuclear localization signals. Studies using in vivo yeast two-hybrid analysis, in vitro protein-protein interactions, and coimmunoprecipitation analyses demonstrated that BR22 formed a protein complex with TTF-1. In vivo cotransfection studies further indicated that BR22 could act with TTF-1 to synergistically activate the SP-B promoter in mammalian cells. Our data suggest that BR22 is a TTF-1-associated protein. Through a protein-protein interaction with TTF-1, BR22 can form a complex and activate the human SP-B promoter in vivo.

Original languageEnglish (US)
Pages (from-to)30-37
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume24
Issue number1
DOIs
StatePublished - 2001

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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