Modulation of human luteinizing hormone β gene transcription by MIP-2A

Asish K. Ghosh, Robert Steele, Ratna B. Ray

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

MIP-2A was recently identified as a MBP-1 interacting cellular protein. We have shown previously that MBP-1 acts as a transcriptional repressor. Functional association between MIP-2A and MBP-1 suggests that MIP-2A can act as a cofactor and relieves MBP-1-mediated transcriptional repression. In this study, we report the tissue-specific expression of MIP-2A and its role in the regulation of gene transcription. RNA dot blot analysis of human multiple tissue expression array suggested that MIP-2A is highly abundant in right cerebellum, pituitary, adrenal, and testis but barely detectable in skeletal muscle. Predominant expression of MIP-2A in pituitary tissue led us to investigate whether MIP-2A can transcriptionally regulate luteinizing hormone β (LHβ), a pituitary-specific hormone synthesized and secreted from gonadotropic cells. The LHβ promoter is regulated by the orphan nuclear receptor SF-1 and homeodomain protein Ptxl. Although each factor enhances the LHβ promoter, coexpression of both results in a strong synergistic activation. Therefore, we examined whether MIP-2A can modulate SF-1- and Ptx1-mediated transcriptional activation. Our results suggested that MIP-2A expression inhibits SF-1- and Ptx1-mediated transactivation of LHβ promoter. Subsequent analysis demonstrated that MIP-2A physically interacts with both SF-1 and Ptxl, thereby inhibiting transactivation of the LHβ promoter. Taken together, our results indicate that MIP-2A preferentially expresses in certain tissues, including the pituitary gland, and negatively regulates the LHβ gene transcription.

Original languageEnglish (US)
Pages (from-to)24033-24038
Number of pages6
JournalJournal of Biological Chemistry
Volume278
Issue number26
DOIs
StatePublished - Jul 27 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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