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)

Early in the development of the imaginal wing disc of Drosophila, the LIM-HD gene tailup (islet), together with the HD genes of the iroquois complex, specify the notum territory of the disc. Later, tailup has been shown to act as a prepattern gene that antagonizes formation of sensory bristles on the notum of this fly. It has been proposed that Tailup downregulates the expression of the proneural genes achaete and scute by interfering with factors needed to activate these genes in the dorsocentral and scutellar regions of the disc. By means of a clonal analysis performed with tailup null alleles, here we show that, on the one hand, tailup is necessary to prevent formation of extra macrochaetae on most of the 11 sites where these landmark bristles arise on the fly notum. On the other hand, tailup is required to activate achaete and scute at the dorsocentral region, probably by acting as an hexameric complex with the cofactor Chip and the transcriptional activator Sspd on the dorsocentral enhancer of the achaete-scute complex. In contrast, in the scutellar region Tailup acts downstream of achaete-scute, antagonizing the proneural function of these genes probably in cooperation with Chip. We conclude that tailup acts on bristle development by several, even antagonistic, mechanisms.
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PMID:The pronotum LIM-HD gene tailup is both a positive and a negative regulator of the proneural genes achaete and scute of Drosophila. 2058 Aug 20

Expression of Mash1 is dysregulated in human neuroblastoma. We have also reported that LMO3 (LIM-only protein 3) has an oncogenic potential in collaboration with neuronal transcription factor HEN2 in neuroblastoma. However, the precise molecular mechanisms of its transcriptional regulation remain elusive. Here we found that LMO3 forms a complex with HEN2 and acts as an upstream mediator for transcription of Mash1 in neuroblastoma. The high levels of LMO3 or Mash1 mRNA expression were significantly associated with poor prognosis in 100 primary neuroblastomas. The up-regulation of Mash1 remarkably accelerated the proliferation of SH-SY5Y neuroblastoma cells, while siRNA-mediated knockdown of LMO3 induced inhibition of growth of SH-SY5Y cells in association with a significant down-regulation of Mash1. Additionally, overexpression of both LMO3 and HEN2 induced expression of Mash1, suggesting that they might function as a transcriptional activator for Mash1. Luciferase reporter assay demonstrated that the co-expression of LMO3 and HEN2 attenuates HES1 (a negative regulator for Mash1)-dependent reduction of luciferase activity driven by the Mash1 promoter. Chromatin immunoprecipitation assay revealed that LMO3 and HEN2 reduce the amount of HES1 recruited onto putative HES1-binding sites and E-box within the Mash1 promoter. Furthermore, both LMO3 and HEN2 are physically associated with HES1 by immunoprecipitation assay. Thus, our present results suggest that a transcriptional complex of LMO3 and HEN2 may contribute to the genesis and malignant phenotype of neuroblastoma by inhibiting HES1 which suppresses the transactivation of Mash1.
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PMID:Oncogenic LMO3 collaborates with HEN2 to enhance neuroblastoma cell growth through transactivation of Mash1. 2157 14


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