The homeodomain coordinates nuclear entry of the Lhx3 neuroendocrine transcription factor and association with the nuclear matrix

Gretchen E. Parker, Ruben M. Sandoval, Hilary A. Feister, Joseph Bidwell, Simon Rhodes

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

LIM homeodomain transcription factors regulate development in complex organisms. To characterize the molecular signals required for the nuclear localization of these proteins, we examined the Lhx3 factor. Lhx3 is essential for pituitary organogenesis and motor neuron specification. By using functional fluorescent derivatives, we demonstrate that Lhx3 is found in both the nucleoplasm and nuclear matrix. Three nuclear localization signals were mapped within the homeodomain, and one was located in the carboxyl terminus. The homeodomain also serves as the nuclear matrix targeting sequence. No individual signal is alone required for nuclear localization of Lhx3; the signals work in combinatorial fashion. Specific combinations of these signals transferred nuclear localization to cytoplasmic proteins. Mutation of nuclear localization signals within the homeodomain inhibited Lhx3 transcriptional function. By contrast, mutation of the carboxyl-terminal signal activated Lhx3, indicating that this region is critical to transcriptional activity and may be a target of regulatory pathways. The pattern of conservation of the nuclear localization and nuclear matrix targeting signals suggests that the LIM homeodomain factors use similar mechanisms for subcellular localization. Furthermore, upon nuclear entry, association of Lhx3 with the nuclear matrix may contribute to LIM homeodomain factor interaction with the other classes of transcription factors.

Original languageEnglish
Pages (from-to)23891-23898
Number of pages8
JournalJournal of Biological Chemistry
Volume275
Issue number31
DOIs
StatePublished - Aug 4 2000

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Nuclear Matrix
Nuclear Localization Signals
Transcription Factors
Mutation
Organogenesis
Motor Neurons
Nuclear Proteins
Neurons
Conservation
Derivatives
Specifications
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

The homeodomain coordinates nuclear entry of the Lhx3 neuroendocrine transcription factor and association with the nuclear matrix. / Parker, Gretchen E.; Sandoval, Ruben M.; Feister, Hilary A.; Bidwell, Joseph; Rhodes, Simon.

In: Journal of Biological Chemistry, Vol. 275, No. 31, 04.08.2000, p. 23891-23898.

Research output: Contribution to journalArticle

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