Modulation of human luteinizing hormone beta gene transcription by MIP-2A.
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.
Ghosh
Asish K
AK
Departments of Pathology, Saint Louis University, St Louis, Missouri 63104, USA.
Steele
Robert
R
Ray
Ratna B
RB
D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins / Q000378:metabolism / Q000502:physiology; D006801:Humans; D037101:Luteinizing Hormone, beta Subunit / Q000096:biosynthesis / Q000235:genetics*; D026901:Membrane Transport Proteins; D051761:Paired Box Transcription Factors; D010902:Pituitary Gland / Q000737:chemistry; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D037101:Luteinizing Hormone, beta Subunit; D026901:Membrane Transport Proteins; D051761:Paired Box Transcription Factors; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; C120759:TRAPPC2 protein, human; D014157:Transcription Factors; C101485:homeobox protein PITX1