The Golgi ribbon is a complex structure of many stacks interconnected by tubules that undergo fragmentation during mitosis through a multistage process that allows correct Golgi inheritance. The fissioning protein CtBP1‐S/BARS (BARS) is essential for this, and is itself required for mitotic entry: a block in Golgi fragmentation results in cell‐cycle arrest in G2, defining the ‘Golgi mitotic checkpoint’. Here, we clarify the precise stage of Golgi fragmentation required for mitotic entry and the role of BARS in this process. Thus, during G2, the Golgi ribbon is converted into isolated stacks by fission of interstack connecting tubules. This requires BARS and is sufficient for G2/M transition. Cells without a Golgi ribbon are independent of BARS for Golgi fragmentation and mitotic entrance. Remarkably, fibroblasts from BARS‐knockout embryos have their Golgi complex divided into isolated stacks at all cell‐cycle stages, bypassing the need for BARS for Golgi fragmentation. This identifies the precise stage of Golgi fragmentation and the role of BARS in the Golgi mitotic checkpoint, setting the stage for molecular analysis of this process.
Inhibition of Golgi fragmentation results in cell cycle arrest at the G2 stage. However, the molecular basis of this G2 block is not known. Here, we show that a block of Golgi partitioning control G2/M progression through the impairment of centrosome recruitment and activation of Aurora-A.
Edited by Daniela CordaKeywords: Golgi Cell cycle Mitosis Membrane and organelle a b s t r a c tIn mammals, the Golgi complex is structured in the form of a continuous membranous system composed of stacks connected by tubular bridges, the ''Golgi ribbon". At the onset of mitosis, the Golgi complex undergoes a multi-step fragmentation process that is required for its correct partition into the dividing cells. Regulation of Golgi fragmentation and cell cycle progression appear to be precisely coordinated. Here, we review recent studies that are revealing the fundamental mechanisms, the molecular players and the biological significance of the mitotic inheritance of the Golgi complex in mammalian cells.
In the present study, we report that the RAS/BRAF/MAP kinase cascade plays a crucial role in the regulation of the Skp2/p27 pathway in thyroid cancer cells and that this is critical for cell proliferation. In vitro studies with cellular models of human thyroid carcinoma cells demonstrated that the adoptive expression of oncogenic RET/PTC1, Ha-RASV12 or BRAFV600E enhances Skp2 and reduces p27 protein expression in a MAP kinase-dependent manner; that RAS/BRAF/MAP kinase-dependent control of p27 expression in thyroid cancer cells occurs by regulating the stability of Skp2 and p27 protein; and that antisense oligonucleotides to p27 suppress growth arrest induced by MEK inhibitors. Finally, analysis of human thyroid carcinomas indicated that MAP kinase-positive thyroid tumors-as detected by immunostaining for p-ERK - presented high p27 degradative activity and low levels of p27 protein (n = 30; p < 0.05). In summary, our results indicate that constitutive signalling of the MAP kinase cascade contributes to the development of thyroid cancer promoted by activated RAS and BRAF oncogenes and that this occurs, at least in part, by compromising the inhibitory function of p27.
Sacred natural sites (SNS) have gained recognition from conservationists, and are regarded as the oldest form of habitat protection in human history. Many case studies and literature reviews have been published on the subject. However, an updated and global-level synthesis on the effect of SNS on biodiversity conservation is still lacking. Here, we provide the first systematic review on SNS and biodiversity conservation, aiming to evaluate the effect of SNS across different: (i) continents; (ii) taxa; (iii) metrics. We checked 2750 papers and by applying inclusion criteria we selected 27 relevant papers. From these, we extracted descriptive data and 131 comparisons between SNS and Reference Sites. We applied vote-counting, multinomial and binomial post-hoc tests to the 131 comparisons. We found strong evidence that SNS have a positive effect on biodiversity, but also strong geographical and taxonomical biases, with most research focusing on Asia and Africa and on plants. We found that SNS have mainly positive effects on taxonomical diversity, vegetation structure and cultural uses of biodiversity. Our results strongly support the view that SNS have positive effects on biodiversity across continents and geographical settings, as found in a number of local studies and earlier overviews. These effects should be given official recognition in appropriate conservation frameworks, together with the specific forms of governance and management that characterize SNS. At the same time, further efforts are also required to fill the geographical and taxonomical gaps here highlighted, and to advancing our knowledge of SNS through more systematic research.
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