antagonist ͉ cancer ͉ Gli ͉ medulloblastoma

Small-molecule inhibition of extracellular proteins that activate membrane receptors has proved to be extremely challenging. Diversity-oriented synthesis and small-molecule microarrays enabled the discovery of robotnikinin, a small molecule that binds the extracellular Sonic Hedgehog (Shh) protein and blocks Shh-signaling in cell lines, human primary keratinocytes and a synthetic model of human skin. Shh pathway activity is rescued by small-molecule agonists of Smoothened, which functions immediately downstream of the Shh receptor Patched.

Epsin (Eps15 interactor) is a cytosolic protein involved in clathrin-mediated endocytosis via its direct interactions with clathrin, the clathrin adaptor AP-2, and Eps15. The NH2-terminal portion of epsin contains a phylogenetically conserved module of unknown function, known as the ENTH domain (epsin NH2-terminal homology domain). We have now solved the crystal structure of rat epsin 1 ENTH domain to 1.8 Å resolution. This domain is structurally similar to armadillo and Heat repeats of β-catenin and karyopherin-β, respectively. We have also identified and characterized the interaction of epsin 1, via the ENTH domain, with the transcription factor promyelocytic leukemia Zn2+ finger protein (PLZF). Leptomycin B, an antifungal antibiotic, which inhibits the Crm1- dependent nuclear export pathway, induces an accumulation of epsin 1 in the nucleus. These findings suggest that epsin 1 may function in a signaling pathway connecting the endocytic machinery to the regulation of nuclear function.

The epsin NH2-terminal homology (ENTH) domain is a membrane interacting module composed by a superhelix of alpha-helices. It is present at the NH2-terminus of proteins that often contain consensus sequences for binding to clathrin coat components and their accessory factors, and therefore function as endocytic adaptors. ENTH domain containing proteins have additional roles in signaling and actin regulation and may have yet other actions in the nucleus. The ENTH domain is structurally similar to the VHS domain. These domains define two families of adaptor proteins which function in membrane traffic and whose interaction with membranes is regulated, in part, by phosphoinositides.

A detailed comparative map of Brassica oleracea and Arabidopsis thaliana has been established based largely on mapping of Arabidopsis ESTs in two Arabidopsis and four Brassica populations. Based on conservative criteria for inferring synteny, "one to one correspondence" between Brassica and Arabidopsis chromosomes accounted for 57% of comparative loci. Based on 186 corresponding loci detected in B. oleracea and A. thaliana, at least 19 chromosome structural rearrangements differentiate B. oleracea and A. thaliana orthologs. Chromosomal duplication in the B. oleracea genome was strongly suggested by parallel arrangements of duplicated loci on different chromosomes, which accounted for 41% of loci mapped in Brassica. Based on 367 loci mapped, at least 22 chromosomal rearrangements differentiate B. oleracea homologs from one another. Triplication of some Brassica chromatin and duplication of some Arabidopsis chromatin were suggested by data that could not be accounted for by the one-to-one and duplication models, respectively. Twenty-seven probes detected three or more loci in Brassica, which represent 25.3% of the 367 loci mapped in Brassica. Thirty-one probes detected two or more loci in Arabidopsis, which represent 23.7% of the 262 loci mapped in Arabidopsis. Application of an EST-based, cross-species genomic framework to isolation of alleles conferring phenotypes unique to Brassica, as well as the challenges and opportunities in extrapolating genetic information from Arabidopsis to Brassica and to more distantly related crops, are discussed.Arabidopsis thaliana, a weed-like member of the Cruciferae family (tribe Sisymbrieae), offers many advantages for basic and applied plant research. These features include small stature, short life cycle, small genome size (2n=10, estimated physical genome size of 100-120 Mb), low frequency of repetitive sequences (∼10% of the nuclear genome; Leutwiler et al. 1984), and prolific seed production. These features, combined with research of the past several decades yielding many mutants, efficient transformation systems, detailed genetic and physical maps, the availability of several P1, YAC, and BAC libraries, and 36,569 public ESTs (http:// www.cbc.umn.edu/ResearchProjects/Arabidopsis), make A. thaliana an ideal model for further molecular and genetic study (Meyerowitz and Somerville 1994). A multinational genome research initiative aiming to completely sequence the Arabidopsis genome by year 2004 (The Multinational Science Steering Committee 1997) is ahead of schedule. Such an accomplishment will undoubtedly create new scientific challenges and opportunities. One of the core issues will be how to apply the information obtained from the Arabidopsis genome project to the improvement of the world's leading crops.The genus Brassica (tribe Brassiceae), including many important crops, is in the same taxonomic family as Arabidopsis thaliana. Such a close relationship suggests that crop plants of the genus Brassica will be among the earliest beneficiaries of a complete sequence of Ara...

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Interest in algae has significantly accelerated with the increasing recognition of their potentially unique role in medical, materials, energy, bioremediation, and synthetic biological research. However, the introduction of tools to study, control, or expand the inner-workings of algae has lagged behind. Here we describe a general molecular method based on guanidinium-rich molecular transporters (GR-MoTrs) for bringing small and large cargos into algal cells. Significantly, this method is shown to work in wild-type algae that have an intact cell wall. Developed using Chlamydomonas reinhardtii , this method is also successful with less studied algae including Neochloris oleoabundans and Scenedesmus dimorphus thus providing a new and versatile tool for algal research.

Doppelfunktion: Die Titelverbindung, ein bereits identifizierter wirksamer Hemmstoff des Hedgehog‐Signalwegs, der embryonischen Zellen notwendige Informationen für die Entwicklung liefert, moduliert die Genexpression von Hedgehog‐Targets, indem sie Mikrotubuli depolymerisiert. Auf diesem Weg wurde eine doppelte Steuerungsfunktion des Zytoskeletts nachgewiesen (siehe Bild).