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Centrosome duplication is critical for cell division, and genome instability can result if duplication is not restricted to a single round per cell cycle. Centrosome duplication is controlled in part by CP110, a centriolar protein that positively regulates centriole duplication while restricting centriole elongation and ciliogenesis. Maintenance of normal CP110 levels is essential, as excessive CP110 drives centrosome over-duplication and suppresses ciliogenesis, whereas its depletion inhibits centriole amplification and leads to highly elongated centrioles and aberrant assembly of cilia in growing cells (1,2). CP110 levels are tightly controlled, partly through ubiquitination by the ubiquitin ligase complex [SCF.sup.cyclin F] during G2 and M phases of the cell cycle (3). Here, using human cells, we report a new mechanism for the regulation of centrosome duplication that requires USP33, a deubiquitinating enzyme that is able to regulate CP110 levels. USP33 interacts with CP110 and localizes to centrioles primarily in S and G2/M phases, the periods during which centrioles duplicate and elongate. USP33 potently and specifically deubiquitinates CP110, but not other cyclin-F substrates. USP33 activity antagonizes [SCF.sup.cyclin F]-mediated ubiquitination and promotes the generation of supernumerary centriolar foci, whereas ablation of USP33 destabilizes CP110 and thereby inhibits centrosome amplification and mitotic defects. To our knowledge, we have identified the first centriolar deubiquitinating enzyme whose expression regulates centrosome homeostasis by countering cyclin-F-mediated destruction of a key substrate. Our results point towards potential therapeutic strategies for inhibiting tumorigenesis associated with centrosome amplification., We recently characterized a novel human CP110-interacting protein, NEURL4, a daughter-centriole-specific protein that inhibits the formation of ectopic microtubule-organizing centres (4). During the course of these studies, NEURL4 was independently [...]

The generalized-stacking-fault-energy (GSFE) curve for pure Cobalt and Co-9 at.% X solid-solution alloys (X = Cr, W, Mo, Ni, Mn, Al, Fe) have been successfully calculated by rigidly shearing an fcc crystal at a (1 1 1) plane along a [1 1 −2] slip direction in two processes using first-principles density-functional-theory (DFT), provide a highly accurate modeling and a fairly good agreement with available experimental and other theoretical results in the literature. The objectives of this study are to provide a useful guideline for the Co-based alloy design with superior performances and new insight for understanding the nature of the fcc to hcp phase transformation. Evaluation of the GSFE values is based on the ratio of the stable and unstable stacking fault energy, the twinnabilities with three criterions for crack tip twinning, grain boundary twinning and inherent twinning, as well as the predicted critical twinning stress. It concludes that alloying with Cr, W and Mo atoms are expected to bring a significant increase in the tendency of the dominant deformation mechanism for the formation of partial dislocations and mechanical twinning of pure Co. The investigation regarding the electronic structure, such as interlayer distance distortion between a faulted and perfect fcc structure, atomic bonding, charge density distributions and density of states (DOS) in the present work can describe why and how alloying atoms change the GSFE values of Co-based alloys. [ABSTRACT FROM AUTHOR]