Nuclear localization domain of thyroid transcription factor-1 in respiratory epithelial cells

Manely Ghaffari, Xin Zeng, Jeffrey A. Whitsett, Cong Yan

Research output: Contribution to journalArticle

45 Scopus citations

Abstract

Thyroid transcription factor-1 (TITF-1) is a homeodomain containing transcription factor that binds to and selectively activates the expression of genes in thyroid and pulmonary epithelial cells. TITF-1 plays a critical role in gene expression and in organogenesis of lung and thyroid. In the present work, epitope-tagged TITF-1 proteins were used to identify the regions of the TITF-1 polypeptide that mediate nuclear localization and transcriptional activity in human lung adenocarcinoma cells. A series of TITF-1-flag deletion mutants was generated and transfected into H441 cells to determine amino acid sequences involved in translocation to the nucleus. Transfection of the TITF-1-flag mutants demonstrated that a nuclear localization signal (NLS) sequence, located at the N-terminus of the homeodomain, is critical for nuclear targeting. The NLS was essential but not sufficient for translocation of TITF-1 to the nucleus, since deletion of the homeodomain itself also blocked nuclear translocation in the presence of NLS. Deletion of the N-terminal transactivation domain of TITF-1 completely abolished its transcriptional activation on the human surfactant protein-B promoter, and deletion of the C-terminal domain partially reduced its stimulatory activity. Nuclear translocation of TITF-1 depends on both an NLS and the homeodomain of the polypeptide. Both C- and N-terminal regions of TITF-1 are involved in transactivation of surfactant protein B gene expression in pulmonary cells.

Original languageEnglish (US)
Pages (from-to)757-761
Number of pages5
JournalBiochemical Journal
Volume328
Issue number3
DOIs
StatePublished - Dec 15 1997
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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