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New work by Elia et al. in this issue of Cell reveals the molecular basis of phosphopeptide recognition by the polo domain and the domain's dual function to promote substrate recognition by targeting the kinase to subcellular structures and to autoregulate the adjacent protein kinase catalytic domain.
The canonical condensin complex (henceforth condensin I) plays an essential role in mitotic chromosome assembly and segregation from yeast to humans. We report here the identification of a second condensin complex (condensin II) from vertebrate cells. Condensins I and II share the same pair of structural maintenance of chromosomes (SMC) subunits but contain different sets of non-SMC subunits. siRNA-mediated...
Tumor necrosis factor (TNFα) receptor signaling can simultaneously activate caspase 8, the transcription factor, NF-κB and the kinase, JNK. While activation of caspase 8 is required for TNFα-induced apoptosis, and induction of NF-κB inhibits cell death, the precise function of JNK activation in TNFα signaling is not clearly understood. Here, we report that TNFα-mediated caspase 8 cleavage and apoptosis...
The mitochondrial ribosome is responsible for the biosynthesis of protein components crucial to the generation of ATP in the eukaryotic cell. Because the protein:RNA ratio in the mitochondrial ribosome (~69:~31) is the inverse of that of its prokaryotic counterpart (~33:~67), it was thought that the additional and/or larger proteins of the mitochondrial ribosome must compensate for the shortened rRNAs...
In the September 26 issue of Science, report that aged yeast cells display high rates of loss of heterozygosity. Furthermore, they show that this reflects an impaired ability to correctly detect and repair DNA double-strand breaks. These results provide insights into how aging can engender genomic instability in eukaryotic cells.
Gram-negative bacterial vesicle formation is a mechanism for specific secretion and transfer of a protein toxin to animals. This discovery should stimulate work on the mechanism of protein sorting into vesicles and the role of vesicles in bacterial pathogenesis.
A tight balance between synaptic vesicle exocytosis and endocytosis is fundamental to maintaining synaptic structure and function. Calcium influx through voltage-gated Ca 2+ channels is crucial in regulating synaptic vesicle exocytosis. However, much less is known about how Ca 2+ regulates vesicle endocytosis or how the endocytic machinery becomes enriched at the nerve terminal...
The structural integrity of mitotic chromosomes is essential for proper chromatid segregation. In this issue of Cell, show that vertebrates contain two distinct condensin complexes, both of which are required for normal mitotic chromosome morphology.
Presynaptic activation of protein kinase A (PKA) induces LTP in cerebellar parallel fiber synapses. Presynaptic LTP is known to require the active zone protein RIM1α, but the underlying induction mechanism remains unclear. We now show that PKA directly phosphorylates RIM1α at two sites. Using paired recordings from cultured cerebellar granule and Purkinje neurons, we demonstrate that LTP is absent...
The ClyA protein is a pore-forming cytotoxin expressed by Escherichia coli and some other enterobacteria. It confers cytotoxic activity toward mammalian cells, but it has remained unknown how ClyA is surface exposed and exported from bacterial cells. Outer-membrane vesicles (OMVs) released from the bacteria were shown to contain ClyA protein. ClyA formed oligomeric pore assemblies in the OMVs, and...
We examined the mechanism responsible for the degradation of p21, a negative regulator of the cell division cycle. We found that p21 proteolysis requires functional ubiquitin and Nedd8 systems. Ubiquitinylated forms of p21 and p21(K0), a p21 mutant missing all lysines, are detected in vivo and in vitro, showing that the presence of lysines is dispensable for p21 ubiquitinylation. Instead, the free...
Polo-like kinases (Plks) perform crucial functions in cell-cycle progression and multiple stages of mitosis. Plks are characterized by a C-terminal noncatalytic region containing two tandem Polo boxes, termed the Polo-box domain (PBD), which has recently been implicated in phosphodependent substrate targeting. We show that the PBDs of human, Xenopus, and yeast Plks all recognize similar phosphoserine/threonine-containing...
Surfactant proteins A and D (SP-A and SP-D) are lung collectins composed of two regions, a globular head domain that binds PAMPs and a collagenous tail domain that initiates phagocytosis. We provide evidence that SP-A and SP-D act in a dual manner, to enhance or suppress inflammatory mediator production depending on binding orientation. SP-A and SP-D bind SIRPα through their globular heads to initiate...
A key step in RNA interference (RNAi) is assembly of the RISC, the protein-siRNA complex that mediates target RNA cleavage. Here, we show that the two strands of an siRNA duplex are not equally eligible for assembly into RISC. Rather, both the absolute and relative stabilities of the base pairs at the 5' ends of the two siRNA strands determine the degree to which each strand participates in the RNAi...
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