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J Biol Chem. 2003 Jun 27;278(26):24033-8. Epub 2003 Apr 16.

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

Author information

1
Departments of Pathology, Saint Louis University, St Louis, Missouri 63104, USA.

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 beta (LHbeta), a pituitary-specific hormone synthesized and secreted from gonadotropic cells. The LHbeta promoter is regulated by the orphan nuclear receptor SF-1 and homeodomain protein Ptx1. Although each factor enhances the LHbeta 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 LHbeta promoter. Subsequent analysis demonstrated that MIP-2A physically interacts with both SF-1 and Ptx1, thereby inhibiting transactivation of the LHbeta promoter. Taken together, our results indicate that MIP-2A preferentially expresses in certain tissues, including the pituitary gland, and negatively regulates the LHbeta gene transcription.

PMID:
12700240
DOI:
10.1074/jbc.M211982200
[Indexed for MEDLINE]
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