Discovering smoking-related pathway alterations in urothelial cell carcinoma pathogenesis

The centrosome serves as the primary micro-tubule-organizing center in animal cells and, consequently, functions in many processes, such as migration and formation of the mitotic spindles. The centrosome consists of a pair of centrioles surrounded by pericentriolar material (PCM), the platform for microtubule nucle-ation. The pair of centrioles duplicate once per cell cycle to ensure the equal segregation of chromosomes in mitosis. The control of centro-some duplication and their capacity to nucle-ate microtubules is tightly coupled to cell cycle progression. Centriole duplication initiates at the beginning of the S phase and the duplicated centrioles elongate until the G 2 phase. At late G 2 phase, the centrosomes mature by recruiting PCM components, resulting in the increase in the microtubule-nucleating capacity that helps the formation of spindle microtubules later in mitosis. PCM recruitment in the centrosome maturation process has been intensively investigated and revealed to be regulated by mitotic kinases. However, the mechanism regulating interphase PCM recruitment remains largely unknown, especially in mammalian cells. in other organisms, centriole duplication factors, C. elegans ZyG-1 1 (Plk4 orthlog) and Drosophila Sas-4 2 (CPAP ortho-log) were demonstrated to be involved in the interphase PCM recruitment. in a recent issue of Cell Cycle, Jeffery et al. 3 proposed that centrosomal protein Centrobin regulates microtubule nucleation and organization by controlling the amount of PCM in interphase. Centrobin was initially identified as a daughter centriole-associated protein required for centriole duplication. 4 Centrobin has been shown to have microtubule-bundling activity 5 and plays a role in the stabilization of mitotic spindles by anchoring them to the centrosome, 6 while the role of Centrobin in interphase cells has not been well-defined. First, Jeffery et al. showed that Centrobin is exclusively localized at centrosomes in inter-phase cells 3 in contrast to its association with spindle microtubules during mitosis. They next showed that when Centrobin is depleted in interphase cells, the microtubules become more focused around the centrosome and sparse in the cell cortex area. Furthermore, microtubules are less stable than those in control cells, as detected by sensitivity to microtubule depolymerizing conditions and by the acetylation state of the microtubules. They further demonstrated that altered micro-tubule organization is caused by increase in the number of short microtubules emanating from the centrosome without changes in the microtubule dynamics. Microtubule nucle-ation depends on the amount and integrity of PCM proteins, and Jeffery et al. observed an increase in the intensity of PCM …