Cell
Of the six glutamate receptor (GIuR) channel subunit families identified by molecular cloning, five have been shown to constitute either the AMPA, kainate, or NMDA receptor channel, whereas the function of the δ subunit family remains unknown. The selective localization of the δ2 subunit of the GluRδ subfamily in cerebellar Purkinje cells prompted us to examine its possible physiological roles by...
Topoisomerase II (topo II) catalyzes the decatenation of interlinked DNA molecules and is essential for chromosome segregation. To test the hypothesis that the noncatalytic C-terminal domain of topo II is necessary for mediating interactions with other proteins required for chromosome segregation, we used a two-hybrid cloning strategy to identify proteins that interact with S. cerevisiae topo II in...
13-type cyclin destruction is necessary for exit from mitosis and the initiation of a new cell cycle. Through the isolation of mutants, we have identified three essential yeast genes, CDC16, CDC23, and CSE1, which are required for proteolysis of the B-type cyclin CLB2 but not of other unstable proteins. cdc23-1 mutants are defective in both entering and exiting anaphase. Their failure to exit anaphase...
The site-specific C to U editing of apolipoprotein B100 (apoB100) mRNA requires a 27 kDa protein (p27) with homology to cytidine deaminase. Here, we show that p27 is a zinc-containing deaminase, which operates catalytically like the E. coli enzyme that acts on monomeric substrate. In contrast with the bacterial enzyme that does not bind RNA, p27 interacts with its polymeric apoB m RNA substrate at...
We have isolated cDNAs and raised antibodies corresponding to the human homologs of the S. cerevisiae CDC27 and CDC16 proteins, which are tetratrico peptide repeat (TPR)-containing proteins essential for mitosis in budding yeast. We find that the CDC27Hs and CDC16Hs proteins colocalize to the centrosome at all stages of the mammalian cell cycle, and to the mitotic spindle. Injection of affinity-purified...
As I hope this review has made clear, mRNA localization plays an important role in directing specific proteins to their correct position within a cell. Although the study of this process is still in its infancy, it is already apparent that there are several ways that mRNAs can be targeted to particular subcellular sites. However, the molecular mechanisms responsible for these different localization...
Cyclin B is degraded at the onset of anaphase by a ubiquitin-dependent proteolytic system. We have fractionated mitotic Xenopus egg extracts to identify components required for this process. We find that UBC4 and at least one other ubiquitin-conjugating enzyme can support cyclin B ubiquitination. The mitotic specificity of cyclin ubiquitination is determined by a 20S complex that contains homologs...
We report the cDNA deduced primary structure of a wheat germ agglutinin-reactive nuclear pore complex (NPC) protein of rat. The protein, termed Nup98 (for nucleoporin of 98 kDa), contains numerous GLFG and FG repeats and some FXFG repeats and is thus a vertebrate member of a family of GLFG nucleoporins that were previously discovered in yeast. Immunoelectron microscopy showed Nup98 to be asymmetrically...
Mutations in HERG cause an inherited cardiac arrhythmia, long OT syndrome (LOT). To define the function of HERG, we expressed the protein in Xenopus oocytes. The biophysical properties of expressed HERG are nearly identical to the rapidly activating delayed rectifier K + current (I K r ) in cardiac myocytes. HERG current is K + selective, declines with depolarizations above...
We have used a combination of genetics and pharmacology to assess the effects of reduced DNA methyltransferase activity on Apc M i n -induced intestinal neoplasia in mice. A reduction in the DNA methyltransferase activity in Min mice due to heterozygosity of the DNA methyltransferase gene, in conjunction with a weekly dose of the DNA methyltransferase inhibitor 5-azadeoxycytidine,...
NIMA is essential for entry into mitosis in Aspergillus nidulans. To examine whether there is a NIMA-like pathway in other eukaryotic cell cycles, we expressed NIMA and its dominant negative mutants in two different eukaryotic systems. In Xenopus oocytes, NIMA induced germinal vesicle breakdown without activating Mos, CDC2, or MAP kinase. In HeLa cells, NIMA induced premature mitotic events without...
Cytochrome cd 1 -nitrite reductase is a bifunctional enzyme that catalyzes the one-electron reduction of nitrite to nitric oxide and the four-electron reduction of oxygen to water. The 1.55 A crystal structure of the dimeric enzyme from Thiosphaera pantotropha is reported here. The protein was sequenced from the X-ray structure. Each subunit contains a covalent c heme with two axial His ligands...
We have identified an essential gene, called FIP1, encoding a 327 amino acid protein interacting with yeast poly(A) polymerase (PAP1) in the two-hybrid assay. Recombinant FIN protein forms a 1:1 complex with PAP in vitro. At 37 o C, a thermosensitive allele of FIP1 shows a shortening of poly(A) tails and a decrease in the steady-state level of actin transcripts. When assayed for 3'-end processing...