Research articles

HERC2 regulates the retention of repair proteins 53BP1, RAP80 and BRCA1 on damaged chromosomes in response to ionizing radiation by forming a complex with the ubiquitin ligases RNF8 and RNF168. Hecr2 deficiency leads to radiosensitivity.

Small RNAs are known to induce heterochromatin formation in various organisms. RNA-dependent mechanisms are shown to be required for the formation of a constitutive heterochromatin structure in the chick.

During germ-cell migration in the zebrafish embryo, Rac1 and RhoA are activated at the cell front where they control formation of actin structures and retrograde flow, respectively. This is imperative for the control of E-cadherin-mediated traction forces that drive single cell migration.

DNA ligase I links newly synthesized DNA fragments. DNA ligase I deficiency causes ubiquitylation of PCNA in yeast and human by the E2 variant Mms26, Ubc47 and the E3 Rad5, which is required for activation of the DNA damage response and cell viability.

In response to CO₂, leaves close their stomatal pores but the CO₂-binding proteins and the cell type responsible for this effect have not been identified. Expression of β-carbonic anhydrase in guard cells modulates the CO₂-mediated regulation of stomatal movements.

Cyclin-dependent kinase 2 (cdk2) is surprisingly found to suppress senescence induced by the Myc oncogene in various cell types. Inactivation or deletion of cdk2 sensitizes mouse embryonic fibroblasts to Myc-induced senescence via a mechanism requiring pRb and p53.

Shigella infection can lead to stimulation of the NF-κB pathway. IpaH9.8, a Shigella effector with ubiquitin ligase activity polyubiquitylates NEMO, a key regulator of NF-κB activation, leading to its degradation and subsequent impairment of NF-κB activation.

The molecular and cellular mechanisms that keep cells apart at compartment boundaries remain unclear. In early Drosophila embryos, cells transiently invade neighbouring compartments, but an actomyosin-based barrier formed of cable-like structures pushes them back into their compartment of origin, in mitotically active epidermis.

Mouse mutants for Sec24b, a component of COPII-coated ER-to-Golgi vesicles, have defects in convergent extension, neural tube closure and other phenotypes related to planar cell polarity (PCP). The PCP component Vangl2 is sorted by Sec24b, and Vangl2 mutants defective in convergent extension do not exit the ER.

The Hippo pathway regulates proliferation and survival in Drosophila and mammals, although shared transcriptional targets of their effectors have not been identified. Mammalian YAP controls expression of the EGFR ligand amphiregulin to regulate epithelial-to-mesenchymal transition in mammary epithelial cells, and the EGFR pathway genetically interacts with Yorkie in Drosophila.

How tunnelling nanotubes form between cells is unclear. A mammalian protein, M-Sec, that has homology to the Sec6 subunit of the exocyst complex, is sufficient and necessary for nanotube formation. The Ral GTPase and its effector, the exocyst complex, are required for M-Sec-dependent regulation of nanotubes.

In differentiating cells, ERK activation shifts from transient to sustained. Quantitative proteomics reveals that, during differentiation, dynamic changes in ERK-interacting proteins regulate the pathway at several levels and by different mechanisms, suggesting a distributed control mechanism for the ERK pathway.

The epithelial-to-mesenchymal transition transcription factor ZEB1 is involved in metastasis. It is now shown to regulate the tumour-initiating capacity of pancreatic and colorectal cancer cells, through the repression of the stemness-inhibiting miR200s, which are found to inhibit the polycomb repressor Bmi-1.

Yeast mating-type switching requires ubiquitylation of the transcriptional repressor α2. This results in removal of α2 from its DNA targets by the ubiquitin-selective AAA-ATPase Cdc48, thus revealing a nuclear function of Cdc48 and an ubiquitin-dependent extraction pathway for dismantling transcription factor—DNA complexes.

Migrating dendritic cells can adapt their adhesive properties to switch between integrin-dependent and -independent modes of migration. By modulating their actin polymerization dynamics, cells can maintain a steady migration speed through a changing environment.

Autophagy is a bulk degradation process that takes place in specialized membrane structures, the origin of which is still unclear. An electron tomography study shows that the ER is connected to the isolation membranes that initiate autophagosome formation in mammalian cells, suggesting that the ER is the membrane source.

Drs2, a phospholipid translocase involved in transport from the trans-Golgi network, is shown to be a new effector of PtdIns(4)P (phosphatidylinositol 4-phosphate). Binding to PtdIns(4)P and to the GTPase exchange factor ARF–GEF, a regulator of Golgi transport, stimulates Drs2 activity.

TAp63, a splice variant of the p53 homologue p63, suppresses tumorigenesis in p53-null mice by mediating Ras oncogene-induced senescence. TAp63-mediated senescence is independent of p53, but requires p21Waf/Cip1 and Rb. TAp63 overrides Ras-driven transformation, while its loss accelerates Ras oncogenesis.

During mitosis, store-operated Ca²⁺ entry (SOCE) is suppressed. Translocation of the ER Ca²⁺ sensor STIM1 to the plasma membrane is critical to SOCE activation, but in mitotic cells STIM1 is phosphorylated and fails to rearrange into near-plasma membrane puncta. Mutation of mitosis-specific phosphorylation sites rescues mitotic SOCE.

IFT20, known to control intraflagellar transport during cilia biogenesis, is also expressed in lymphoid and myeloid non-ciliated cells. IFT20 is localized to the secretory pathway in T-lymphocytes and translocates to the immune synapse on antigen engagement to modulate the recycling of T-cell receptors.