Interacting selectively and non-covalently with messenger RNA (mRNA), an intermediate molecule between DNA and protein. mRNA includes UTR and coding sequences, but does not contain introns.
Vascular endothelial growth factor (VEGF) is an angiogenic cytokine, which plays a major role in tumor angiogenesis. VEGF mRNA expression is controlled by hypoxia, growth factors and hormones through both transcriptional and post-transcriptional mechanisms. VEGF mRNA has a short half-life and its abundance is regulated by the binding of stabilizing (HuR, hRNP-L) and still uncharacterised destabilizing proteins to its 3'-untranslated region. Here, we report that the ACTH-regulated zinc-finger protein TIS11b and its homologs TIS11 and TIS11d interact with the 3'-untranslated region of VEGF mRNA and decrease its stability (half-life reduced from 130 to 60 min). Within the 2201 bp 3'-untranslated region of VEGF mRNA, we identified a 75 bp domain, containing two consensus AU-rich motifs, which binds TIS11b and mediates its destabilizing activity. Ribonucleoprotein (RNP) complex immunoprecipitation experiments allowed us to demonstrate that the interaction between TIS11b and VEGF 3'-untranslated region occurs in live cells. Knocking down TIS11b expression in primary adrenocortical cells with small interfering (si)RNAs clearly indicated that TIS11b participates in the control of both basal and, to a larger extent, ACTH-induced VEGF mRNA expression levels. TIS11b is the first VEGF mRNA-destabilizing protein identified so far and therefore appears as a new potential target in antiangiogenic therapies.
Interacting selectively and non-covalently with any protein or protein complex (a complex of two or more proteins that may include other nonprotein molecules).
Evidence
1:
Inferred from Physical InteractionIntAct
Systematic mapping of protein-protein interactions, or 'interactome' mapping, was initiated in model organisms, starting with defined biological processes and then expanding to the scale of the proteome. Although far from complete, such maps have revealed global topological and dynamic features of interactome networks that relate to known biological properties, suggesting that a human interactome map will provide insight into development and disease mechanisms at a systems level. Here we describe an initial version of a proteome-scale map of human binary protein-protein interactions. Using a stringent, high-throughput yeast two-hybrid system, we tested pairwise interactions among the products of approximately 8,100 currently available Gateway-cloned open reading frames and detected approximately 2,800 interactions. This data set, called CCSB-HI1, has a verification rate of approximately 78% as revealed by an independent co-affinity purification assay, and correlates significantly with other biological attributes. The CCSB-HI1 data set increases by approximately 70% the set of available binary interactions within the tested space and reveals more than 300 new connections to over 100 disease-associated proteins. This work represents an important step towards a systematic and comprehensive human interactome project.
Interacting selectively and non-covalently with a specific DNA sequence in order to modulate transcription. The transcription factor may or may not also interact selectively with a protein or macromolecular complex.
BRF1 (Butyrate response factor 1) is a member of an immediate early gene family specifying putative nuclear transcription factors. A repeat motif incorporating two Cys and two His is highly conserved between family members identified from yeast, Drosophila, mouse, rat, and human. The chromosome localization of none of the human genes has been determined thus far. Using the polymerase chain reaction on a human-rodent hybrid panel, we have localized BRF1 to chromosome 14. This was confirmed by direct sequencing of the PCR fragment. Using fluorescence in situ hybridization, the chromosome localization of BRF1 was further determined as 14q22-q24.
A major pathway of degradation of nuclear-transcribed mRNAs that proceeds through a series of ordered steps that includes poly(A) tail shortening and that can regulate mRNA stability.
Vascular endothelial growth factor (VEGF) is an angiogenic cytokine, which plays a major role in tumor angiogenesis. VEGF mRNA expression is controlled by hypoxia, growth factors and hormones through both transcriptional and post-transcriptional mechanisms. VEGF mRNA has a short half-life and its abundance is regulated by the binding of stabilizing (HuR, hRNP-L) and still uncharacterised destabilizing proteins to its 3'-untranslated region. Here, we report that the ACTH-regulated zinc-finger protein TIS11b and its homologs TIS11 and TIS11d interact with the 3'-untranslated region of VEGF mRNA and decrease its stability (half-life reduced from 130 to 60 min). Within the 2201 bp 3'-untranslated region of VEGF mRNA, we identified a 75 bp domain, containing two consensus AU-rich motifs, which binds TIS11b and mediates its destabilizing activity. Ribonucleoprotein (RNP) complex immunoprecipitation experiments allowed us to demonstrate that the interaction between TIS11b and VEGF 3'-untranslated region occurs in live cells. Knocking down TIS11b expression in primary adrenocortical cells with small interfering (si)RNAs clearly indicated that TIS11b participates in the control of both basal and, to a larger extent, ACTH-induced VEGF mRNA expression levels. TIS11b is the first VEGF mRNA-destabilizing protein identified so far and therefore appears as a new potential target in antiangiogenic therapies.
BRF1 (Butyrate response factor 1) is a member of an immediate early gene family specifying putative nuclear transcription factors. A repeat motif incorporating two Cys and two His is highly conserved between family members identified from yeast, Drosophila, mouse, rat, and human. The chromosome localization of none of the human genes has been determined thus far. Using the polymerase chain reaction on a human-rodent hybrid panel, we have localized BRF1 to chromosome 14. This was confirmed by direct sequencing of the PCR fragment. Using fluorescence in situ hybridization, the chromosome localization of BRF1 was further determined as 14q22-q24.
Any process that modulates the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of proteins by the translation of mRNA.
The process in which a precursor cell type acquires the specialized features of a T cell via a differentiation pathway dependent upon transit through the thymus.
A reference proteome is a set of protein sequences derived from a complete proteome which constitutes a defined standard for a particular user community. Reference proteomes are manually defined according to a number of criteria. They cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical and biotechnological research. Reference proteomes have been selected to provide broad coverage of the tree of life, and constitute a representative cross-section of the taxonomic diversity to be found within UniProtKB.
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