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Substrate specificity in ubiquitylation is conferred by ubiquitin ligases (E3s). Now, several ways that E3s can interact to mediate ubiquitylation are illustrated for Ubr1 (a RING finger E3) and Ufd4 (a HECT domain E3), in Saccharomyces cerevisiae. These interactions and the related concept of E4 activity are discussed.
The histone H3 variant CENP-A defines centromeric chromatin, but it has been unclear how CENP-A is stably maintained at centromeres. It has now been shown that the CENP-A licensing factor HsKNL2 and the small GTPases activating protein MgcRacGAP cooperate to promote the stability of newly loaded CENP-A at centromeres.
In the United States, enrolment in graduate degree programmes in the biological sciences has risen sharply during the global economic downturn, but new graduates face an uncertain job market. What can prospective and current students do to ensure that a graduate degree remains a sound investment?
Cytoplasmic dynein drives vesicular transport from the periphery to the cell body of neurons. Missense mutations in the dynein tail domain cause neurodegenerative disease in mouse models. New data on the effect of one such dynein mutation provide insight into the intramolecular communication and flexible stepping of this essential cellular motor.
Oscillating activities of actomyosin networks at the apical side of epithelial cells have been linked to morphogenesis in Drosophila. Montell and colleagues show that myosin oscillations on a polarised actin network at basal cell surfaces of follicle epithelial cells are also required for Drosophila egg chamber elongation.
Calcineurin signalling or pressure overload is shown to lead to cardiac hypertrophy through NFAT-mediated increase in miR-199. miR-199 inhibits the Dyrk1a kinase, which leads to further activation of NFAT. Inhibition of miR-199 reverses hypertrophy and fibrosis in mouse models of cardiac failure.
Cyclic AMP is known to affect RAF–MEK–ERK signalling, but the precise mechanism has remained unknown. An interaction between AKAP-Lbc and the scaffolding protein KSR1 is now shown to tie cAMP production to ERK pathway regulation.
IRGM is a human GTPase that triggers autophagy in response to pathogen infection. On Mycobacteria infection, IRGM binds the mitochondrial cardiolipin to induce mitochondrial fission and a general autophagy response. It can also trigger autophagy-independent mitochondria-mediated cell death.
Legs-at-odd-angles (Loa) mutations in cytoplasmic dynein tail have been linked to neurodegeneration in mice although how they affect dynein function has remained unclear. Biochemical, live-cell imaging and modelling techniques now show that loa mutations affect the motor run-length in vitro and in vivo as well as altering motor domain coordination.
The histone H3 variant CENP-A defines centromeric chromatin, but it is not known how it is maintained at these loci. The CENP-A licensing factor HsKNL2, the small GTPases Cdc42 and Rac, and their regulators Ect2 and MgcRacGAP, coordinately promote the stability of newly loaded CENP-A at centromeres.
EFA-6, originally identified as a suppressor of defects associated with dynein muations in early Caenorhabditis elegans embryos, regulates microtubule growth at the embryo cortex through a conserved amino-terminal motif but independently of its ARF6 GTP exchange factor activity.
Two pathways in ubiquitylation are linked, as the RING domain E3 ligase Ubr1, from the N-end rule pathway, is found to bind and cooperate with the HECT domain E3 Ufd4 from the ubiquitin-fusion degradation pathway.
The transcriptional regulation of haematopoietic stem cell quiescence is only starting to be understood. The nuclear transcription factor Nurr1 drives early haematopoietic progenitors into quiescence through the upregulation of the quiescence factor p18/INK4C.
The Nek2 kinase directs the separation of duplicated centrosomes. Now the Hippo pathway components hSav1 and Mst2 are shown to regulate the function of Nek2 at the centrosome. This pathway cooperates with the kinesin Eg5 to mediate centrosome separation.
Normal migrating cells exhibit contact inhibition of locomotion (CIL) when meeting a neighbouring cell, but metastatic cancer cells lose this inhibition. Interactions btween ephrin and ephrin receptors are now shown to underlie CIL in migrating cells.
Uncapped telomeres activate a p53-mediated DNA damage response to elicit cellular senescence. In turn, p53 negatively modulates telomere capping by promoting ubiquitin-mediated degradation of the TRF2 shelterin component.
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