Suchergebnisse

The specific binding of regulatory proteins to DNA sequences exhibits no clear patterns of association between amino acids (AAs) and nucleotides (NTs). This complexity of protein-DNA interactions raises the question of whether a simple set of wide-coverage recognition rules can ever be identified. Here, we analyzed this issue using the extensive LacI family of transcriptional factors (TFs). We searched for recognition patterns by introducing a new approach to phylogenetic footprinting, based on the pervasive presence of local regulation in prokaryotic transcriptional networks. We identified a set of specificity correlations -determined by two AAs of the TFs and two NTs in the binding sites- that is conserved throughout a dominant subgroup within the family regardless of the evolutionary distance, and that act as a relatively consistent recognition code. The proposed rules are confirmed with data of previous experimental studies and by events of convergent evolution in the phylogenetic tree. The presence of a code emphasizes the stable structural context of the LacI family, while defining a precise blueprint to reprogram TF specificity with many practical applications © 2010 Camas et al. ; This work was supported by a Spanish Government Formación de Profesorado Universitario fellowship (to F.M.C.), Ministerio de Ciencia e Innovación grant BFU2008-03632/BMC (to J.F.P), and Comunidad de Madrid grant CCG08-CSIC/SAL-3651 (to J.F.P). ; Peer Reviewed

The EU Framework 5 REGIA (Regulatory Gene Initiative in Arabidopsis) Consortium, comprising 29 laboratories, was established to investigate transcription factor gene function in Arabidopsis. As part of the REGIA project, the present study describes the characterisation, in terms of sequence, expression and function, of two members of the plant-specific AP2/ERF transcription factor family: AP2.76 and AP2.72. Phylogenetic analyses of their predicted amino acid sequences placed AP2.76 in the DRE/CRT subgroup, members of which bind the DRE/CRT cis-acting element and AP2.72 in the ERF subgroup, members of which bind the GCC-box cis-acting promoter element. On the basis of the observed sequences similarities and predicted DNA binding specificities, AP2.76 was hypothesised to function in an abiotic stress signalling pathway while AP2.72 was hypothesized to function in a pathogen response pathway. ; TARA (Trinity's Access to Research Archive) has a robust takedown policy. Please contact us if you have any concerns: rssadmin@tcd.ie

The growth arrest-specific gene 1 (Gas1) protein has been proposed to function during development as an inhibitor of growth and a mediator of cell death and is also re-expressed in adult neurons during excitotoxic insult. Here we have demonstrated that the Gas1 protein shows high structural similarity to the glial cell-derived neurotrophic factor (GDNF) family receptors α, which mediate GDNF responses through the receptor tyrosine kinase Ret. We found that Gas1 binds Ret in a ligand-independent manner and sequesters Ret in lipid rafts. Signaling downstream of Ret is thus modified through a mechanism that involves the adaptor protein Shc as well as ERK, eventually blocking Akt activation. Consequently, when Gas1 is induced, Ret-mediated GDNF-dependent survival effects are compromised. ; This work was supported in part by grants from the Madrid regional government (to B. M.), the Direcion General Investigacion Cientifica Tecnica, and the Human Frontiers program (to J. R. N.). The Department of Immunology and Oncology was founded and is supported by the Spanish National Research Council and by Pfizer. ; Peer reviewed

BASED ON ALL LEGISLATORS WHO VOLUNTARILY LEFT THE ARKANSAS LEGISLATURE OVER THE LAST TWELVE YEARS, THIS STUDY SUGGESTS THAT FAMILY FACTORS EXPLAIN MORE DEPARTURES THAN DO FINANCIAL CONSIDERATIONS.