Cell
phyllopod (phyl) encodes a novel protein required for fate determination of photoreceptors R1, R6, and R7, the last three photoreceptors to be recruited into the ommatidia of the developing Drosophila eye. Genetic data suggests that phyl acts downstream of Ras1, raf, and yan to promote neuronal differentiation in this subset of photoreceptors. Ectopic expression of phyl in the cone cell precursors...
Uptake and release of Ca 2 + from isolated liver nuclei were studied with fluorescent probes. We show with the help of digital imaging and confocal microscopy that the Ca 2 + -sensitive fluorescent probe Fura 2 is concentrated in or around the nuclear envelope and that the distribution of Fura 2 fluorescence is similar to that of an endoplasmic reticulum marker. The previously...
The phyllopod (phyl) gene regulates the fates of a subset of cells in the developing Drosophila eye; in the absence of phyl function, the R1, R6, and R7 photoreceptors are transformed into additional cone cells, whereas ectopic phyl expression in the cone cell precursors transforms these cells into additional R7 cells. Within this group of cells, phyl expression thus mimics activation of the Raf pathway...
Recent biochemical and genetic studies indicate that in addition to the octamer-binding proteins Oct-1 and Oct-2, other B cell components are required for lymphoid-restricted, octamer site-mediated immunoglobulin gene promoter activity. Using a genetic screen in yeast, we have isolated B cell-derived cDNAs encoding Oct-binding factor 1 (OBF-1), a novel protein that specifically associates with Oct-1...
The cytoplasmic C-terminus of Epstein-Barr virus (EBV) latent infection membrane protein 1 (LMP1) is essential for B lymphocyte growth transformation and is now shown to interact with a novel human protein (LMP1-associated protein 1 [LAP1]). LAN is homologous to a murine protein, tumor necrosis factor receptor-associated factor 2 (TRAF2), implicated in growth signaling from the p80 TNFR. A second...
Identifying mutations that cause specific osteochon-drodysplasias will provide novel insights into the function of genes that are essential for skeletal morphogenesis. We report here that an autosomal dominant form of Stickler syndrome, characterized by mild spondyloepiphyseal dysplasia, osteoarthritis, and sensorineural hearing loss, but no eye involvement, is caused by a splice donor site mutation...
Analysis of interspecies matings between S. typhimurium and E. coli indicates that the genetic barrier that separates these (and perhaps many other) related species is primarily recombinational. The structural component of this barrier is genomic sequence divergence. The mismatch repair enzymes act as potent inhibitors of interspecies recombination, whereas the SOS system acts as an inducible positive...
Aging in S. cerevisiae is exemplified by the fixed number of cell divisions that mother cells undergo (termed their life span). We have exploited a correlation between life span and stress resistance to identify mutations in four genes that extend life span. One of these, SIR4, encodes a component of the silencing apparatus at HM loci and telomeres. The sir4-42 mutation extends life span by more than...
GAP-43 has been termed a ''growth'' or ''plasticity'' protein because it is expressed at high levels in neuronal growth cones during development and during axonal regeneration. By homologous recombination, we generated mice lacking GAP-43. The mice die in the early postnatal period. GAP-43-deficient retinal axons remain trapped in the chiasm for 6 days, unable to navigate past this midline decision...
IL-1β-converting enzyme (ICE) cleaves pro-1L-1β to generate mature IL-1β. ICE is homologous to other proteins that have been implicated in apoptosis, including CED-3 and Nedd-2/Ich-1. We generated ICE-deficient mice and observed that they are overtly normal but have a major defect in the production of mature IL-1β after stimulation with lipopolysaccharide. IL-1α production is also impaired. ICE-deficient...
SH-PTP2, the vertebrate homolog of Drosophila corkscrew, associates with several activated growth factor receptors, but its biological function is unknown. We assayed the effects of injection of wild-type and mutant SH-PTP2 RNAs on Xenopus embryogenesis. An internal phosphatase domain deletion (ΔP) acts as a dominant negative mutant, causing severe posterior truncations. This phenotype is rescued...
Of the several families of adhesion receptors involved in leukocyte-endothelial cell interactions, only the selectins have been shown to initiate leukocyte interaction under physiologic shear; indeed, β2 (CD18) integrins responsible for neutrophil arrest are unable to engage without prior selectin-mediated rolling. In contrast, α4 (CD49d) integrins are shown here to initiate lymphocyte contact (''tethering'')...
The HIV-1 matrix (MA) protei n contains two subcellular localization signals with opposing effects. A myristoylated N-terminus governs particle assembly at the plasma membrane, and a nucleophilic motif facilitates import of the viral preintegration complex into the nucleus of nondividing cells. Here, we show that myristoylation acts as the MA dominant targeting signal in HIV-1 producer cells. During...
Mice that are homozygous for the autosomal recessive chondrodysplasia (cho) mutation die at birth with abnormalities in cartilage of limbs, ribs, mandible, and trachea. Limb bones of newborn cho/cho mice are wider at the metaphyses than normal bones and only about half the normal length. By linkage analysis, the cho gene and the gene encoding the α1 (XI) chain of cartilage collagen XI were mapped...
The 2.5 A resolution structure of a cocrystal containing the paired domain from the Drosophila paired (prd) protein and a 15 by site shows structually independent N-terminal and C-terminal subdomains. Each of these domains contains a helical region resembling the homeodomain and the Hin recombinase. The N-terminal domain makes extensive DNA contacts, using a novel β turn motif that binds in the minor...