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It has been proposed that the spindle assembly checkpoint detects both unattached kinetochores and lack of tension between sister kinetochores when sister chromatids are not attached to opposite spindle poles. However, here we argue that there is only one signal — whether kinetochores are attached to microtubules or not — and this has implications for our understanding of both chromosome segregation and the control of genomic stability.
The epithelial–mesenchymal transition (EMT) occurs in pre-metastatic cancer cells and is also associated with the acquisition of stem-cell-like characteristics. A molecular link between EMT and stemness now emerges with the finding that Bmi1, a polycomb protein that promotes self-renewal of certain stem-cell populations, is a direct transcriptional target of the EMT inducer, Twist1.
Distinct stem-cell populations are known to reside in hypoxic niches during development and postnatal life. Hypoxia-inducible transcription factors (HIFs) directly regulate the Wnt/β-catenin pathway to ensure the maintenance of both adult and embryonic stem cells.
Pumilio proteins PUM1 and PUM2 are shown to regulate microRNA-dependent gene silencing by induction of a conformational switch in the 3′ untranslated region of p27 mRNA. This conformational change is required for efficient microRNA-mediated repression of this cell-cycle regulator in rapidly proliferating cells.
Transcriptional noise has an important role in generating diversity in cellular populations that are seemingly identical. As this noise stems from the inherent stochasticity of gene expression, it has been unclear whether it is directly controlled. Dig1, a regulator of the budding yeast mating pathway, is now shown to prevent transcriptional noise by regulating the spatial organization of downstream gene targets.
The conserved vertebrate transcriptional repressor Tel regulates angiogenesis by directly controlling endothelial sprouting through modulation of Notch ligand Dll4 and vessel branching through other angiogenesis factors such as sprouty and VE-cadherin
Notch and vascular endothelial growth factor receptor (VEGFR) coordinates endothelial cells behaviour during angiogenesis sprouting although exactly how is uncertain. Endothelial cells dynamically compete for the leading position in a sprout through relative levels of Vegfr1 and Vegfr2 in a Notch dependent manner.
In yeast, the MAPK-responsive protein Dig1 regulates Ste12 transcription factor activity in response to pheromone. Dig1 is now shown to prevent long-range interchromosomal interactions between Ste12-target genes, dampening transcriptional 'noise'.
The ubiquitin ligase RACO-1 is found to be a co-factor for the AP-1 transcription factor c-Jun, and its depletion reduces AP-1 target gene expression, proliferation and tumour formation. RACO-1 is stabilised by growth factors through the MEK/ERK pathway, which promotes K63 linked ubiquitylation, opposing the K48-linked proteolytic auto-ubiquitylation of RACO-1.
SCFFbw7 mediates the ubiquitylation and degradation of Myc. Now, Myc is also shown to be stabilized by ubquitylation through SCFβ-TrCP. During recovery from S phase arrest, SCFβ-TrCP mediates the addition of a polyubiquitin chain on the Myc amino terminus that is functionally distinct from that formed by Fbw7.
The transcription factor Twist1 interacts with the Bmi1 polycomb group protein. This complex is proposed to regulate the epithelial–mesenchymal transition and the tumour-initiating capability of head-and-neck squamous cell carcinoma cells.
The Prdm16 transcription factor is expressed preferentially in stem cells of the nervous- and the haematopoietic-system and is required for their maintenance. Prdm16 is shown to regulate reactive oxygen species (ROS) levels in the nervous system through an effect on the hepatocyte growth Factor (HGF) promoter.
Low oxygen levels are observed in the niche of some stem cells. The hypoxic transcription factor HIF-1 directly regulates Wnt signalling to ensure stem cells maintenance in these niches.
Quiescent cells contain high levels of both the cell cycle inhibitor p27, and the miRNAs that should negatively regulate it. In response to growth factor, the RNA-binding protein PUM1 interacts with the 3′UTR of p27 to induce a structural change leading to miRNA-mediated downregulation of p27.
