The Infona portal uses cookies, i.e. strings of text saved by a browser on the user's device. The portal can access those files and use them to remember the user's data, such as their chosen settings (screen view, interface language, etc.), or their login data. By using the Infona portal the user accepts automatic saving and using this information for portal operation purposes. More information on the subject can be found in the Privacy Policy and Terms of Service. By closing this window the user confirms that they have read the information on cookie usage, and they accept the privacy policy and the way cookies are used by the portal. You can change the cookie settings in your browser.
The PML protein induces senescence, and, upon oncogenic stress, its absence promotes cellular transformation. In this issue of Cell, Scaglioni et al. (2006) show that phosphorylation of PML by CK2, a kinase frequently activated in human cancers, promotes PML degradation. Therefore, pharmacological inhibition of CK2-induced PML loss could be used to offset tumor establishment.
Half of hereditary nonpolyposis colon cancer kindreds harbor mutations that inactivate MutLα (MLH1•PMS2 heterodimer). MutLα is required for mismatch repair, but its function in this process is unclear. We show that human MutLα is a latent endonuclease that is activated in a mismatch-, MutSα-, RFC-, PCNA-, and ATP-dependent manner. Incision of a nicked mismatch-containing DNA heteroduplex by this four-protein...
Cortical representations of visual information are modified by an animal's visual experience. To investigate the mechanisms in mice, we replaced the coding part of the neural activity-regulated immediate early gene Arc with a GFP gene and repeatedly monitored visual experience-induced GFP expression in adult primary visual cortex by in vivo two-photon microscopy. In Arc-positive GFP heterozygous mice,...
In this issue of Cell, Axel and colleagues (Lomvardas et al., 2006) report that a single enhancer of an odorant receptor (OR) gene cluster interacts with multiple OR gene promoters on different chromosomes. This study suggests a mechanism that allows olfactory sensory neurons to choose randomly and express only one out of more than 1000 OR genes.
The mismatch repair process corrects errors in newly synthesized DNA. In this issue, Modrich and colleagues (Kadyrov et al., 2006) show that a component of the human mismatch repair machinery, MutLα, has endonuclease activity. MutLα introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXOI to degrade the strand containing the mismatch.
Regulatory T cells suppress autoimmune responses to self-antigens. Recent studies, including one in this issue of Cell (Wu et al., 2006), suggest that the ability of T cells to choose between launching a productive immune response, functional inactivation, or developing into regulatory T cells depends upon the interplay of the key transcriptional regulators FOXP3 and NFAT.
Knocking down expression of disease-related genes using small interfering RNAs (siRNAs) has potential for treating a variety of illnesses. This Essay will examine the opportunities for harnessing RNA interference (RNAi) for therapy, as well as the obstacles and possible ways to circumvent them.
Cytoplasmic dynein, the 1.2 MDa motor driving minus-end-directed motility, has been reported to move processively along microtubules, but its mechanism of motility remains poorly understood. Here, using S. cerevisiae to produce recombinant dynein with a chemically controlled dimerization switch, we show by structural and single-molecule analysis that processivity requires two dynein motor domains...
Minimal hammerhead ribozymes have been characterized extensively by static and time-resolved crystallography as well as numerous biochemical analyses, leading to mutually contradictory mechanistic explanations for catalysis. We present the 2.2 Å resolution crystal structure of a full-length Schistosoma mansoni hammerhead ribozyme that permits us to explain the structural basis for its 1000-fold catalytic...
The PML tumor suppressor controls key pathways for growth suppression, induction of apoptosis, and cellular senescence. PML loss occurs frequently in human tumors through unknown posttranslational mechanisms. Casein kinase 2 (CK2) is oncogenic and frequently upregulated in human tumors. Here we show that CK2 regulates PML protein levels by promoting its ubiquitin-mediated degradation dependent on...
Antigen stimulation of immune cells activates the transcription factor NFAT, a key regulator of T cell activation and anergy. NFAT forms cooperative complexes with the AP-1 family of transcription factors and regulates T cell activation-associated genes. Here we show that regulatory T cell (Treg) function is mediated by an analogous cooperative complex of NFAT with the forkhead transcription factor...
The expression of a single odorant receptor (OR) gene from a large gene family in individual sensory neurons is an essential feature of the organization and function of the olfactory system. We have used chromosome conformation capture to demonstrate the specific association of an enhancer element, H, on chromosome 14 with multiple OR gene promoters on different chromosomes. DNA and RNA fluorescence...
Mechanical tension controls the function of a wide variety of eukaryotic motor proteins. Single-molecule analyses have revealed how some of these proteins sense and respond to tension. The single motor studies on dynein by Reck-Peterson et al. (2006) described in this issue pave the way to understand molecular mechanisms used by this unique machine.
During meiosis, crossing-over—the exchange of genetic material between maternal and paternal chromosomes—is stringently controlled to restrict the number of crossovers per chromosome pair. In this issue of Cell, Martini et al. (2006) report that the reduction of crossover-initiating events does not result in fewer crossovers. These results have important implications for our understanding of crossover...
How the ER-associated degradation (ERAD) machinery accurately identifies terminally misfolded proteins is poorly understood. For luminal ERAD substrates, this recognition depends on their folding and glycosylation status as well as on the conserved ER lectin Yos9p. Here we show that Yos9p is part of a stable complex that organizes key components of ERAD machinery on both sides of the ER membrane,...
Development and homeostasis of the cardiovascular system require intimate interactions between endothelial and smooth muscle cells, which form a seamless circulatory network. We show that histone deacetylase 7 (HDAC7) is specifically expressed in the vascular endothelium during early embryogenesis, where it maintains vascular integrity by repressing the expression of matrix metalloproteinase (MMP)...
Small RNAs are essential for cell integrity, regulating gene expression at the levels of translation, RNA degradation, and chromatin. A series of recent reports show that the germlines of mammals and flies contain unique classes of small RNAs with potential functions in spermatogenesis and genome stability. Another study explores how tissue-specific expression of a small RNA is achieved. Together...
Crossovers produced by homologous recombination promote accurate chromosome segregation in meiosis and are controlled such that at least one forms per chromosome pair and multiple crossovers are widely spaced. Recombination initiates with an excess number of double-strand breaks made by Spo11 protein. Thus, crossover control involves a decision by which some breaks give crossovers while others follow...
Set the date range to filter the displayed results. You can set a starting date, ending date or both. You can enter the dates manually or choose them from the calendar.