These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Functional regions of the homeodomain protein IDX-1 required for transactivation of the rat somatostatin gene.
    Author: Lu M, Miller C, Habener JF.
    Journal: Endocrinology; 1996 Jul; 137(7):2959-67. PubMed ID: 8770920.
    Abstract:
    The insulin-, glucagon- and somatostatin-producing cells (beta, alpha, and delta, respectively) in the pancreatic islets derive from a common precursor stem cell and differentiate sequentially during embryonic development. The homeodomain protein islet duodenum HOX (IDX)-1 [insulin promoter factor (IPF)-1/somatostatin transactivating factor (STF)-1)] is a transcription factor critically required for both the development of the pancreas and the transcriptional expression of the insulin gene. IDX-1 may also act to determine the differentiation of the common pancreatic precursor to beta, alpha, and delta cells. Although IDX-1 is detected in most adult mouse islet beta-cells and regulates insulin gene transcription, it is also found in 15% of the delta-cells and transactivates the rat somatostatin gene. The roles of different domains of IDX-1 involved in the transactivation of the somatostatin gene are unclear. In this study, we have created a series of amino- and carboxy-terminal deletions, as well as point substitution mutations to delineate functional domains within the IDX-1 protein. We find that deletions amino-proximal to the homeodomain enhance DNA-binding to the TAAT-1 transcriptional control element within the somatostatin gene promoter. However, these amino-terminal deletions result in substantial decreases in transactivation of a transcriptional reporter containing the TAAT-1 element. Paradoxically, coexpression of the transcriptionally inactive, amino-terminally deleted IDX-1 mutant proteins, either with the wild-type IDX-1 or with themselves, results in a marked enhancement of transactivation of the transcriptional TAAT-1 element reporter. We provide evidence that this synergistic enhancement of transactivation is mediated by protein-protein interactions among the regions of IDX-1 located carboxyl-proximal to the homeodomain. Although successive deletions into the carboxy-terminal region do not alter DNA-binding, these deletions result in a biphasic enhancement and diminution of transactivation. The IDX-1 homeodomain mediates sequence- specific DNA-binding because substitution mutations within this region abolish DNA-binding. All of the amino- and carboxy-terminal deletion proteins were present in nuclear extracts of transfected cells, suggesting that nuclear localization signals reside within the IDX-1 homeodomain. The mapping of the functional domains of IDX-1 may facilitate understanding of IDX-1-mediated gene regulation and islet cell development.
    [Abstract] [Full Text] [Related] [New Search]