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Different kinases and phosphatases control the triggering of T-cell receptors. This signaling network is now reconstituted in vitro with CD3ζ, Lck, CD45, Csk and liposomes. Rigorous quantitative analyses reveal how the system is maintained in a quiescent state and how the kinase-phosphatase balance can be modulated by different events to allow activation in an ultrasensitive manner.
A long intergenic noncoding RNA, Firre, is now shown to localize to a domain across its own chromosomal locus and to distinct interacting transchromosomal loci in mouse and human cells. In addition, Firre interacts with nuclear-matrix factor hnRNPU. These results lead to a model in which Firre functions as a nuclear-organization factor modulating the topological organization of multiple chromosomes.
Rpn11, the only essential deubiquitinase (DUB) of the 26S proteasome, sits at the top of the substrate entry pathway and facilitates substrate degradation through cotranslocational deubiquitination. The structure of the Rpn11–Rpn8 complex, together with functional assays, offers insight into Rpn11's promiscuous DUB activity during proteasomal degradation.
A new study identifies the splicing factor SRSF6 as a proto-oncogene frequently overexpressed in human skin cancer. SRSF6-overexpressing mice develop skin hyperplasia and aberrant alternative splicing, with SRSF6 binding to alternative exons of the pre-mRNA of the extracellular-matrix protein tenascin C, thus promoting expression of isoforms characteristic of invasive and metastatic cancer.
Cancer cells often exhibit hyperactive signaling pathways. A new study now shows that Plcγ1 competes with Grb2 for binding to the fibroblast growth factor receptor 2 (FGFR2) in nonstimulated cells. Reduction in Grb2 expression results in increased Plcγ1 activity and cell motility, thus providing a molecular basis for the observation that reduced Grb2 expression correlates with metastatic potential.
The voltage-sensing domain (VSD) of voltage-gated ion channels transitions from a resting to an activated conformation upon membrane polarization. EPR spectroscopy analysis has now determined the position of the KvAP VSD in a resting conformation, revealing a new ‘tilt-shift’ model for transitioning between resting and activated states.
Transcription termination correlates with the loss of Tyr1 phosphorylation from the C-terminal domain (CTD) of Rpb1, an event thought to be necessary for the recruitment of termination factors. The phosphatase Glc7, an integral component of the cleavage-and-polyadenylation factor (CPF), is now shown to dephosphorylate Tyr1 and to contribute to termination in vivo.
Autorepression of PER-encoding genes underlies the periodic fluctuations in expression that drive the circadian clock. New work shows that histone deacetylase and histone methyltransferase activities are sequentially recruited to promoters of PER-encoding genes by separate PER protein–containing complexes and repress transcription via histone H3K9 modifications at those targets.
Some cancer cells lacking telomerase activity extend their telomeres via an alternative, recombination-based mechanism, termed ALT. A new study shows that depletion of histone chaperone ASF1 can induce ALT in both primary and cancer cells, suggesting that the ALT pathway may be triggered by changes in chromatin state.
The long-awaited crystal structure of Saccharomyces cerevisiae DNA polymerase ε reveals a unique domain never before observed in B-family DNA polymerases. This novel domain endows polymerase ε with a capacity for highly processive DNA synthesis.
The exosome complex has key roles in RNA processing and quality control. Single-particle EM analyses now provide compelling evidence for two distinct pathways by which substrate RNAs can pass through the exosome structure to reach the catalytic site for exonuclease digestion.