Role of the LXXLL-motif and activation function 2 domain in subcellular localization of Dax-1 (dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1)

Kaname Kawajiri, Togo Ikuta, Taiga Suzuki, Masatomo Kusaka, Masami Muramatsu, Kenji Fujieda, Masayoshi Tachibana, Ken-Ichirou Morohashi

Research output: Contribution to journalArticle

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Abstract

Dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1 (Dax-1, NR0B1) is an orphan nuclear receptor that represses transcription by Ad4 binding protein/steroidogenic factor I (Ad4BP/SF-1, NR5A1). Observations on human diseases and the phenotypes of mice, in which the corresponding genes have been disrupted, have elucidated essential roles of these two nuclear receptors in differentiation of steroidogenic tissues. However, little is known about how the functions of these factors are regulated. Here we have examined their subcellular localization and have clarified the molecular mechanisms regulating subcellular localization of Dax-1. Prompted by the finding that nuclear localization of Dax-1 correlates with the presence of Ad4BP/SF-1 in the early stages of pituitary development, we have tested the possibility that interaction between the two factors is essential for the nuclear localization of Dax-1. In vitro studies with cultured cells demonstrated that an interaction involving the LXXLL motifs in the N-terminal repeat region of Dax-1 plays a key role in its subcellular localization. In addition, we found that a mutant form of DAX-1 (L466R), from a patient with adrenal hypoplasia congenita, was defective in nuclear localization in spite of having an intact N terminus. Taken together, the results reveal that the subcellular localization of Dax-1 is influenced by the presence of Ad4BP/SF-1, and that two regions of Dax-1 have important roles for this process.

Original languageEnglish
Pages (from-to)994-1004
Number of pages11
JournalMolecular Endocrinology
Volume17
Issue number6
DOIs
Publication statusPublished - Jun 1 2003

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X-Linked Genes
Chromosomes, Human, Pair 1
Steroidogenic Factor 1
Orphan Nuclear Receptors
Terminal Repeat Sequences
Cytoplasmic and Nuclear Receptors
Cell Communication
Cultured Cells
Phenotype
Genes
Dosage-sensitive sex reversal
X-linked adrenal hypoplasia congenita
In Vitro Techniques

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Endocrinology

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Role of the LXXLL-motif and activation function 2 domain in subcellular localization of Dax-1 (dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1). / Kawajiri, Kaname; Ikuta, Togo; Suzuki, Taiga; Kusaka, Masatomo; Muramatsu, Masami; Fujieda, Kenji; Tachibana, Masayoshi; Morohashi, Ken-Ichirou.

In: Molecular Endocrinology, Vol. 17, No. 6, 01.06.2003, p. 994-1004.

Research output: Contribution to journalArticle

Kawajiri, Kaname ; Ikuta, Togo ; Suzuki, Taiga ; Kusaka, Masatomo ; Muramatsu, Masami ; Fujieda, Kenji ; Tachibana, Masayoshi ; Morohashi, Ken-Ichirou. / Role of the LXXLL-motif and activation function 2 domain in subcellular localization of Dax-1 (dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome, gene 1). In: Molecular Endocrinology. 2003 ; Vol. 17, No. 6. pp. 994-1004.
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