 Paul W. Howard
Ph.D., University of Iowa, 1995
Assistant Professor, Cell and Developmental Biology
My studies are focused on the role of Lhx proteins in regulating transcription with special emphasis on the role of LIM interacting proteins. Lim homeodomain (Lhx) transcription factors are critical regulators of development. The importance of these proteins in the development of many organs and structures is demonstrated by the analysis of mutant organisms ranging from flatworms to humans. Lhx proteins contain a conserved sequence specific DNA binding structure known as a homeodomain. In addition these proteins contain two LIM domains at the amino terminus. A LIM domain consists of two zinc finger structures and occurs in a variety of proteins in both the cytoplasm and the nucleus. The LIM domain is thought to be a protein interaction domain and there are many examples of proteins known to interact with Lhx protein LIM domains. For example in the fruit fly Drosophila melonogaster the regulated interaction of the LIM interacting protein CHIP with the Lhx protein apterous is required for proper wing development. Through the use of a yeast protein interaction screen we have recently cloned a LIM interacting protein named selective lim binding (SLB) protein that interacts specifically with the Lhx proteins Lhx3 and Lhx4. This specificity of interaction is in contrast to the well-studied LIM interacting protein CHIP and its mammalian homolog, nuclear LIM interacter (NLI). CHIP/NLI binds with high affinity to all nuclear LIM domains tested.
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| McGee Creek Ridge, Mt. Hood |
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In addition to being necessary for proper development of the pituitary in mice and humans Lhx3, Lhx4, and other Lhx proteins likely play a critical role in the proper transcriptional control of several peptide hormone genes in the adult pituitary. We are using pituitary hormone gene expression as a model system to study Lhx protein functions. Lhx proteins appear to play a role in the ability of these genes to respond to extracellular signals. We are approaching these studies with a combination of in vitro analysis, transciptional studies in cultured cell lines, and through the use of transgenic mice. The goal of these studies is to delineate the role of Lhx proteins and their interacting partners in regulating transcription.
Recent publications:
Howard, P. W., and R. A. Maurer (2000) Identification of a Conserved Protein that Interacts with Specific LIM Homeodomain Transcription Factors. J. Biol. Chem. 275, 13336-13342.
Howard, P. W., and R. A. Maurer (2001) A Point Mutation in the LIM Domain of Lhx3 Reduces Activation of the Glycoprotein Hormone a-Subunit Promoter. J. Biol. Chem. 276, 19020-19026.
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