Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
Cancer stem cell activity may not merely be an intrinsic characteristic of a subset of cancer cells and could be regulated by environmental cues. High Wnt activity in human colorectal cancer designates a tumour-initiating population and is orchestrated by the microenvironment.
The calcium-binding protein CRACR2A positively regulates the activity of CRAC channels. CRACR2A is a ternary complex which binds to, and stabilizes, the interaction between STIM1 and Orai1, and disassociates as intracellular calcium levels rise.
A complex containing the oncogene Myc, Skp2 E3 ligase and the coactivators Miz1 and p300 promotes transcription of RhoA. Overexpression of this complex increases RhoA levels and is detected in metastatic human cancers.
Cytoplasmic polyadenylation-driven translational control is known to regulate the expression of stored maternal mRNA in meiosis and early embryonic divisions. CPEB proteins mediate cell cycle phase-specific changes in polyadenylation that are also required for cell proliferation and mitotic entry in other actively dividing cells.
Motile cilia direct efficient, oriented flow, which is ensured by alignment of their beating. In mammalian brain ventricles, coupling between hydrodynamic forces and the planar cell polarity protein Vangl2 allows cilia that have docked in random orientation to reorient in a uniform direction.
Twenty-two microRNAs are found to be amplified or deleted in hepatocellular carcinoma (HCC). miR-151 is encoded by an intron in the focal adhesion kinase FAK-1 gene, with which it is co-transcribed, and increases HCC cell migration in vitro and invasion in vivo by directly targeting RhoGDIA. miR-151 amplification correlates with HCC metastasis.
How membrane deformation and actin remodelling are coordinated to generate functional transport vesicles remains poorly understood. ARF1 coordinates clathrin coat recruitment and actin polymerization by binding the clathrin heavy chain binding protein, CYFIP, and facilitates Rac1-dependent actin polymerization to generate transport carriers at the trans-Golgi network.
Oncogene expression can induce permanent cell-cycle arrest by activating the p53 pathway. BRD7 positively regulates p53 transcriptional activity in this context by interacting with p300 and stimulating acetylation of both p53 and histones.
The core kinetochore protein CENP-H is shown to be required for the organization of the metaphase plate. CENP-H regulates microtubule plus-end dynamics, and chromosome oscillations, which are shown to be essential for chromosome congression.
A new link is reported between regulators of endosomal trafficking and cytokinesis. Production of the phosphoinositide lipid PI3P at the midbody triggers the KIF13A-mediated recruitment of the centrosomal proteins FYVE-CENT and TTC19 to the division site. TTC19 may in turn regulate abscission by control of the ESCRTIII complex.
BPLF1 is a viral NEDD8-specific protease that binds to cullin-based ubiquitin ligases and regulates the turnover of their substrates. By inducing the accumulation of the licensing factor CDT1, BPLF1 ensures efficient replication of the viral genome and has a key role in the virus life cycle.
The 17–92 miRNA cluster promotes tumourigenesis although the identity of the specific miRNA responsible for this effect has been unclear. MiR-19 is sufficient to promote Notch induced T-cell associated leukaemia in vivo and a shRNA screen for genes that phenocopy miR-19 effects identifies PI3-K regulators as miR-19 target genes.
miRNAs can both promote and repress tumorigenesis, and directly control epithelial–mesenchymal transition (EMT). miR-9 (which is upregulated in breast cancer cells) is activated by MYC and MYCN, and regulates EMT and metastasis through direct control of E-cadherin. In contrast, tumour angiogenesis is controlled indirectly through effects on vascular endothelial growth factor (VEGF) expression.
Impaired turnover of the autophagy substrate p62 leads to liver injury. p62 inhibits the ubiquitin ligase Keap1, leading to stabilization of the transcription factor Nrf2. High levels of p62 in autophagy deficient animals leads to unusually high expression of Nrf2 targets genes and results in liver injury.
A prostate cancer epigenome map reveals that genes are suppressed in clusters through long-range epigenetic silencing (LRES). Regions of LRES contain known tumour suppressors and miRNAs, and may expand to neighbouring genes during tumour progression.
In response to parathyroid hormone (PTH), TGF-β type II receptor (TβRII) directly phosphorylates the PTH type I receptor (PTH1R) and modulates PTH-induced endocytosis of a PTH1R/TβRII complex. Mice that lack TβRII display higher bone mass — a phenotype similar to that observed in mice expressing a constitutively active version of PTH1R.
In postnatal skeletal muscle, satellite cells are resident myogenic progenitors responsible for muscle growth and regeneration. A distinct population of muscle-resident stem cells that localizes in the interstitium and expresses the factor PW1 is identified. These cells are myogenic and contribute to muscle regeneration in vivo.
In budding yeast, many inducible genes translocate to the nuclear periphery when activated. Sequence motifs have now been identified in promoters, which target genes to the nuclear periphery and contribute to gene activation
The E3 ubiquitin ligase Parkin mediates the clearance of depolarized mitochondria through the autophagy pathway. PINK1 kinase activity is required for Parkin translocation to depolarized mitochondria where Parkin generates polyubiquitin chains on the voltage-dependent anion channel (VDAC1) to recruit the autophagic adaptor p62/SQSTM1.
Hedgehog signalling and activation of its downstream effectors Gli1/2 is deregulated in tumorigenesis. Hedgehog-induced HDAC1 is shown to activate Gli1/2 through its deacetylation. This effect is negatively regulated by the Cullin3/RENKCTD11 ubiquitin ligase, a Gli antagonist that is often lost in human medulloblastoma.