Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hypothalamus is a key regulatory unit of the neuroendocrine system and plays an essential role in energy balance and reproduction. Despite its important role, the molecular mechanisms underlying hypothalamic development are not fully understood. Here, we report molecular analyses of a newly identified murine homeobox gene, Bsx/Bsx1a, that is expressed in the developing and postnatal hypothalamus. We demonstrate that BSX1A is a DNA binding protein and a transcriptional activator. Transcriptional reporter assays identified the C-terminal region of BSX1A as an activation domain. We have isolated an alternative splice form of Bsx1a, designated Bsx1b, which retains the N-terminal region but lacks the homeodomain. Analyses of subcellular localization using transfected cell lines revealed that BSX1A and BSX1B localize in the nuclei and cytoplasm, respectively. Immunohistochemical analyses suggested that both BSX1A and BSX1B are expressed in the neonatal hypothalamus. Taking these data together, we propose that alternative RNA splicing is involved in hypothalamic development/function.
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PMID:Cloning and functional analysis of hypothalamic homeobox gene Bsx1a and its isoform, Bsx1b. 1735 77

Otx proteins are involved in the induction of neurectoderm patterning and morphogenetic movements, leading to the formation of the vertebrate central nervous system. Despite lack of homology of sequence outside the homeodomain, a large body of evidence has shown that the Otx/Otd class of proteins has similar functions in many animal phyla. Thus, characterization of functional domains in proteins of this family would help in understanding how this functional equivalence operates. Our previous analysis using the zebrafish embryo (Bellipanni et al., 2000, Dev Biol 223:339-353), has suggested that induction of cell aggregation is a morphoregulatory role of Otx/Otd factors in embryonic development. We now use the induction of cell aggregation as an in vivo assay to examine the functional requirement for particular domains of the zOtx1 protein. We demonstrate that zOtx1 induces cell aggregation by acting as a transcriptional activator through its C-terminal region. Further, we show that a region of 37 amino acids in the C-terminal third of zOtx1 is necessary but not sufficient for this activation potential. The effects of selective deletion of each of the three homeodomain alpha-helices of zOtx1 on cell aggregation were also tested. Surprisingly, we find that helix 3, which is required for binding to DNA, is dispensable for stimulation of cell aggregation. Our results suggest that for transcriptional activation of at least one gene in the cell aggregation pathway, zOtx1 need not bind directly to DNA, but does require helix 1 and 2 of its homeodomain to interact with an as yet undefined DNA binding protein.
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PMID:Molecular dissection of Otx1 functional domains in the zebrafish embryo. 1989 Aug 51

ZEBRA is a site-specific DNA binding protein that functions as a transcriptional activator and as an origin binding protein. Both activities require that ZEBRA recognizes DNA motifs that are scattered along the viral genome. The mechanism by which ZEBRA discriminates between the origin of lytic replication and promoters of EBV early genes is not well understood. We explored the hypothesis that activation of replication requires stronger association between ZEBRA and DNA than does transcription. A ZEBRA mutant, Z(S173A), at a phosphorylation site and three point mutants in the DNA recognition domain of ZEBRA, namely Z(Y180E), Z(R187K) and Z(K188A), were similarly deficient at activating lytic DNA replication and expression of late gene expression but were competent to activate transcription of viral early lytic genes. These mutants all exhibited reduced capacity to interact with DNA as assessed by EMSA, ChIP and an in vivo biotinylated DNA pull-down assay. Over-expression of three virally encoded replication proteins, namely the primase (BSLF1), the single-stranded DNA-binding protein (BALF2) and the DNA polymerase processivity factor (BMRF1), partially rescued the replication defect in these mutants and enhanced ZEBRA's interaction with oriLyt. The findings demonstrate a functional role of replication proteins in stabilizing the association of ZEBRA with viral DNA. Enhanced binding of ZEBRA to oriLyt is crucial for lytic viral DNA replication.
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PMID:A subset of replication proteins enhances origin recognition and lytic replication by the Epstein-Barr virus ZEBRA protein. 2080 3

The WRKY proteins are a major family of plant transcription factors implicated in the regulation of plant defense mechanisms against pathogens. OsWRKY6 was isolated based on expression profiling data carried out with samples infected by Xanthomonas oryzae pv. oryzae (Xoo). OsWRKY6 encodes a DNA binding protein that contains one WRKY domain, a nuclear localization signal and C(2)H(2)-type zinc finger motif. OsWRKY6 is a member of the group II family of WRKY proteins. Based on the result of yeast one hybrid assay this OsWRKY6 protein binds to the typical W box ((T)TGACC/T). OsWRKY6 functions as a transcriptional activator in yeast. OsWRKY6 enhanced the expression of the reporter gene downstream of OsPR1 promoter, indicating that OsWRKY6 is a transcriptional activator in rice as well. Heterologous expression of OsWRKY6 enhanced disease resistance to pathogen. Defense-related genes were constitutively expressed in Arabidopsis transgenic lines overexpressing OsWRKY6. All together, OsWRKY6 functions as a positive transcriptional regulator of the plant defense response.
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PMID:Heterologous expression of OsWRKY6 gene in Arabidopsis activates the expression of defense related genes and enhances resistance to pathogens. 2176 43

Among the many abnormally expressed proteins in ovarian cancer, the prominent cancer in women, ID1 (inhibitors of DNA binding protein 1) is a potential one among other several targets. Interaction of ID1 with ETS-1 (transcriptional activator of p16(INK4a)) suppresses the transcription of p16(INK4a) and causes abnormal cell proliferation. A peptide aptamer (ID1/3-PA7) has been designed to prevent this interaction and thereby leading to the transcription of p16(INK4a). However, the structural basis behind the molecular interaction of ID1 with ETS-1 (agonist) and ID1/3-PA7 (antagonist) is poorly understood. In order to understand this structural recognition and their interaction mechanism, in silico methods were used. From this interaction analysis, the residues of ETS-1 involved in interaction with the p16(INK4a) promoter were found to be targeted by ID1. Subsequently, ETS-1 binding residues of ID1 were found to be targeted by its aptamer- ID1/3-PA7. These results suggest that both ETS-1 and ID1/3-PA7 binds at the same region harbored by the residues-H97, D100, R103, D104, L107, A144, C145, D149, D150 and C154 of ID1. All these observations correlate with the experimental reports, suggesting that the identified residues might play a crucial role in promulgating the oncogenic effects of ID1. In silico alanine scanning mutagenesis also confirms the role of identified hot spot residues in p16(INK4a) regulation. Finally, the molecular dynamic simulation studies reveal the prolonged stability of the aforementioned interacting complexes. The obtained results throw light on the structure and residues of ID1 involved in transcriptional regulation of p16(INK4a).
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PMID:Structural insights into interacting mechanism of ID1 protein with an antagonist ID1/3-PA7 and agonist ETS-1 in treatment of ovarian cancer: molecular docking and dynamics studies. 2271 36


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