Subnuclear partitioning and functional regulation of the Pit-1 transcription factor

Maureen G. Mancini, Bing Liu, Z. Dave Sharp, Michael A. Mancini

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Subnuclear compartmentation is postulated to play an important role in many aspects of nuclear metabolism. To directly test an application of this model to transcription factor function, we examined the subnuclear partitioning behavior of Pit-1, a tissue-specific, POU-class transactivator. Biochemical and in situ assays indicate the nuclear pool of Pit-1 is normally divided between two compartments: the majority being differentially soluble in detergent, and a significant insoluble fraction (~20%) bound to the nuclear matrix. Examination of Pit-1 deletion mutants and chimeric fusions reveal the highly conserved 66 amino acid POU-specific domain contains a necessary and sufficient nuclear matrix targeting signal. The nuclear partitioning behavior of several natural or engineered point mutations of Pit-1 was also examined. Surprisingly, the inactive point mutants were completely matrix-bound, irrespective of their ability to bind Pit-1 specific DNA. These results suggest that dynamic partitioning of Pit-1 is a component of its normal transactivator function that takes place upon the insoluble nuclear substructure where transcription occurs.

Original languageEnglish (US)
Pages (from-to)322-338
Number of pages17
JournalJournal of Cellular Biochemistry
Volume72
Issue number3
DOIs
StatePublished - Mar 1 1999

Keywords

  • Nuclear matrix
  • Pituitary
  • Protein-protein interaction
  • RNA metabolism
  • Transcription

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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